ProfessorJaspalKooner

Tan ST, Scott W, Panoulas V, Sehmi J, Zhang W, Scott J, Elliott P, Chambers J, Kooner JSet al., 2014, Coronary heart disease in Indian Asians., Global Cardiology Science & Practice, Vol: 2014, Pages: 13-23, ISSN: 2305-7823

The Indian Asian population accounts for a fifth of all global deaths from coronary heart disease (CHD). CHD deaths on the Indian subcontinent have doubled since 1990, and are predicted to rise a further 50% by 2030. Reasons underlying the increased CHD mortality among Indian Asians remain unknown. Although conventional cardiovascular risk factors contribute to CHD in Indian Asians as in other populations, these do not account for their increased risk. Type-2 diabetes, insulin resistance and related metabolic disturbances are more prevalent amongst Indian Asians than Europeans, and have been proposed as major determinants of higher CHD risk among Indian Asians. However, this view is not supported by prospective data. Genome-wide association studies have not identified differences in allele frequencies or effect sizes in known loci to explain the increased CHD risk in Indian Asians. Limited knowledge of mechanisms underlying higher CHD risk amongst Indian Asians presents a major obstacle to reducing the burden of CHD in this population. Systems biology approaches such as genomics, epigenomics, metabolomics and transcriptomics, provide a non-biased approach for discovery of novel biomarkers and disease pathways underlying CHD. Incorporation of these 'omic' approaches in prospective Indian Asian cohorts such as the London Life Sciences Population Study (LOLIPOP) provide an exciting opportunity for the identification of new risk factors underlying CHD in this high risk population.

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Al-Hussaini A, Kooner JS, John C, 2013, Novel Metabolic Biomarkers Predict Cardiovascular Mortality, Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7322

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Do R, Willer CJ, Schmidt EM, Sengupta S, Gao C, Peloso GM, Gustafsson S, Kanoni S, Ganna A, Chen J, Buchkovich ML, Mora S, Beckmann JS, Bragg-Gresham JL, Chang H-Y, Demirkan A, Den Hertog HM, Donnelly LA, Ehret GB, Esko T, Feitosa MF, Ferreira T, Fischer K, Fontanillas P, Fraser RM, Freitag DF, Gurdasani D, Heikkila K, Hyppoenen E, Isaacs A, Jackson AU, Johansson A, Johnson T, Kaakinen M, Kettunen J, Kleber ME, Li X, Luan J, Lyytikainen L-P, Magnusson PKE, Mangino M, Mihailov E, Montasser ME, Mueller-Nurasyid M, Nolte IM, O'Connell JR, Palmer CD, Perola M, Petersen A-K, Sanna S, Saxena R, Service SK, Shah S, Shungin D, Sidore C, Song C, Strawbridge RJ, Surakka I, Tanaka T, Teslovich TM, Thorleifsson G, Van den Herik EG, Voight BF, Volcik KA, Waite LL, Wong A, Wu Y, Zhang W, Absher D, Asiki G, Barroso I, Been LF, Bolton JL, Bonnycastle LL, Brambilla P, Burnett MS, Cesana G, Dimitriou M, Doney ASF, Doering A, Elliott P, Epstein SE, Eyjolfsson GI, Gigante B, Goodarzi MO, Grallert H, Gravito ML, Groves CJ, Hallmans G, Hartikainen A-L, Hayward C, Hernandez D, Hicks AA, Holm H, Hung Y-J, Illig T, Jones MR, Kaleebu P, Kastelein JJP, Khaw K-T, Kim E, Klopp N, Komulainen P, Kumari M, Langenberg C, Lehtimaki T, Lin S-Y, Lindstrom J, Loos RJF, Mach F, McArdle WL, Meisinger C, Mitchell BD, Mueller G, Nagaraja R, Narisu N, Nieminen TVM, Nsubuga RN, Olafsson I, Ong KK, Palotie A, Papamarkou T, Pomilla C, Pouta A, Rader DJ, Reilly MP, Ridker PM, Rivadeneira F, Rudan I, Ruokonen A, Samani N, Scharnagl H, Seeley J, Silander K, Stancakova A, Stirrups K, Swift AJ, Tiret L, Uitterlinden AG, van Pelt LJ, Vedantam S, Wainwright N, Wijmenga C, Wild SH, Willemsen G, Wilsgaard T, Wilson JF, Young EH, Zhao JH, Adair LS, Arveiler D, Assimes TL, Bandinelli S, Bennett F, Bochud M, Boehm BO, Boomsma DI, Borecki IB, Bornstein SR, Bovet P, Burnier M, Campbell H, Chakravarti A, Chambers JC, Chen Y-DI, Collins FS, Cooper RS, Danesh J, Dedoussis G, de Faire U, Feranil AB, Ferrieres J, Ferrucci L, Freet al., 2013, Common variants associated with plasma triglycerides and risk for coronary artery disease, Nature Genetics, Vol: 45, Pages: 1345-1352, ISSN: 1061-4036

Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 × 10−8 for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

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Willer CJ, Schmidt EM, Sengupta S, Peloso GM, Gustafsson S, Kanoni S, Ganna A, Chen J, Buchkovich ML, Mora S, Beckmann JS, Bragg-Gresham JL, Chang H-Y, Demirkan A, Den Hertog HM, Do R, Donnelly LA, Ehret GB, Esko T, Feitosa MF, Ferreira T, Fischer K, Fontanillas P, Fraser RM, Freitag DF, Gurdasani D, Heikkila K, Hyppoenen E, Isaacs A, Jackson AU, Johansson A, Johnson T, Kaakinen M, Kettunen J, Kleber ME, Li X, Luan J, Lyytikainen L-P, Magnusson PKE, Mangino M, Mihailov E, Montasser ME, Mueller-Nurasyid M, Nolte IM, O'Connell JR, Palmer CD, Perola M, Petersen A-K, Sanna S, Saxena R, Service SK, Shah S, Shungin D, Sidore C, Song C, Strawbridge RJ, Surakka I, Tanaka T, Teslovich TM, Thorleifsson G, Van den Herik EG, Voight BF, Volcik KA, Waite LL, Wong A, Wu Y, Zhang W, Absher D, Asiki G, Barroso I, Been LF, Bolton JL, Bonnycastle LL, Brambilla P, Burnett MS, Cesana G, Dimitriou M, Doney ASF, Doering A, Elliott P, Epstein SE, Eyjolfsson GI, Gigante B, Goodarzi MO, Grallert H, Gravito ML, Groves CJ, Hallmans G, Hartikainen A-L, Hayward C, Hernandez D, Hicks AA, Holm H, Hung Y-J, Illig T, Jones MR, Kaleebu P, Kastelein JJP, Khaw K-T, Kim E, Klopp N, Komulainen P, Kumari M, Langenberg C, Lehtimaki T, Lin S-Y, Lindstrom J, Loos RJF, Mach F, McArdle WL, Meisinger C, Mitchell BD, Mueller G, Nagaraja R, Narisu N, Nieminen TVM, Nsubuga RN, Olafsson I, Ong KK, Palotie A, Papamarkou T, Pomilla C, Pouta A, Rader DJ, Reilly MP, Ridker PM, Rivadeneira F, Rudan I, Ruokonen A, Samani N, Scharnagl H, Seeley J, Silander K, Stancakova A, Stirrups K, Swift AJ, Tiret L, Uitterlinden AG, van Pelt LJ, Vedantam S, Wainwright N, Wijmenga C, Wild SH, Willemsen G, Wilsgaard T, Wilson JF, Young EH, Zhao JH, Adair LS, Arveiler D, Assimes TL, Bandinelli S, Bennett F, Bochud M, Boehm BO, Boomsma DI, Borecki IB, Bornstein SR, Bovet P, Burnier M, Campbell H, Chakravarti A, Chambers JC, Chen Y-DI, Collins FS, Cooper RS, Danesh J, Dedoussis G, de Faire U, Feranil AB, Ferrieres J, Ferrucci L, Freimer NBet al., 2013, Discovery and refinement of loci associated with lipid levels, Nature Genetics, Vol: 45, Pages: 1274-1283, ISSN: 1061-4036

Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10−8, including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.

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O'Seaghdha CM, Wu H, Yang Q, Kapur K, Guessous I, Zuber AM, Koettgen A, Stoudmann C, Teumer A, Kutalik Z, Mangino M, Dehghan A, Zhang W, Eiriksdottir G, Li G, Tanaka T, Portas L, Lopez LM, Hayward C, Lohman K, Matsuda K, Padmanabhan S, Firsov D, Sorice R, Ulivi S, Brockhaus AC, Kleber ME, Mahajan A, Ernst FD, Gudnason V, Launer LJ, Mace A, Boerwinckle E, Arking DE, Tanikawa C, Nakamura Y, Brown MJ, Gaspoz J-M, Theler J-M, Siscovick DS, Psaty BM, Bergmann S, Vollenweider P, Vitart V, Wright AF, Zemunik T, Boban M, Kolcic I, Navarro P, Brown EM, Estrada K, Ding J, Harris TB, Bandinelli S, Hernandez D, Singleton AB, Girotto G, Ruggiero D, d'Adamo AP, Robino A, Meitinger T, Meisinger C, Davies G, Starr JM, Chambers JC, Boehm BO, Winkelmann BR, Huang J, Murgia F, Wild SH, Campbell H, Morris AP, Franco OH, Hofman A, Uitterlinden AG, Rivadeneira F, Voelker U, Hannemann A, Biffar R, Hoffmann W, Shin S-Y, Lescuyer P, Henry H, Schurmann C, Munroe PB, Gasparini P, Pirastu N, Ciullo M, Gieger C, Maerz W, Lind L, Spector TD, Smith AV, Rudan I, Wilson JF, Polasek O, Deary IJ, Pirastu M, Ferrucci L, Liu Y, Kestenbaum B, Kooner JS, Witteman JCM, Nauck M, Kao WHL, Wallaschofski H, Bonny O, Fox CS, Bochud Met al., 2013, Meta-analysis of genome-wide association studies identifies six new loci for serum calcium concentrations, PLoS Genetics, Vol: 9, Pages: 1-13, ISSN: 1553-7390

Calcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based cohorts and investigated the 14 most strongly associated loci in ≤21,679 additional individuals. Seven loci (six new regions) in association with serum calcium were identified and replicated. Rs1570669 near CYP24A1 (P = 9.1E-12), rs10491003 upstream of GATA3 (P = 4.8E-09) and rs7481584 in CARS (P = 1.2E-10) implicate regions involved in Mendelian calcemic disorders: Rs1550532 in DGKD (P = 8.2E-11), also associated with bone density, and rs7336933 near DGKH/KIAA0564 (P = 9.1E-10) are near genes that encode distinct isoforms of diacylglycerol kinase. Rs780094 is in GCKR. We characterized the expression of these genes in gut, kidney, and bone, and demonstrate modulation of gene expression in bone in response to dietary calcium in mice. Our results shed new light on the genetics of calcium homeostasis.

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Sabater-Lleal M, Huang J, Chasman D, Naitza S, Dehghan A, Johnson AD, Teumer A, Reiner AP, Folkersen L, Basu S, Rudnicka AR, Trompet S, Malarstig A, Baumert J, Bis JC, Guo X, Hottenga JJ, Shin S-Y, Lopez LM, Lahti J, Tanaka T, Yanek LR, Oudot-Mellakh T, Wilson JF, Navarro P, Huffman JE, Zemunik T, Redline S, Mehra R, Pulanic D, Rudan I, Wright AF, Kolcic I, Polasek O, Wild SH, Campbell H, Curb JD, Wallace R, Liu S, Eaton CB, Becker DM, Becker LC, Bandinelli S, Raikkonen K, Widen E, Palotie A, Fornage M, Green D, Gross M, Davies G, Harris SE, Liewald DC, Starr JM, Williams FMK, Grant PJ, Spector TD, Strawbridge RJ, Silveira A, Sennblad B, Rivadeneira F, Uitterlinden AG, Franco OH, Hofman A, van Dongen J, Willemsen G, Boomsma DI, Yao J, Jenny NS, Haritunians T, McKnight B, Lumley T, Taylor KD, Rotter JI, Psaty BM, Peters A, Gieger C, Illig T, Grotevendt A, Homuth G, Voelzke H, Kocher T, Goel A, Franzosi MG, Seedorf U, Clarke R, Steri M, Tarasov KV, Sanna S, Schlessinger D, Stott DJ, Sattar N, Buckley BM, Rumley A, Lowe GD, McArdle WL, Chen M-H, Tofler GH, Song J, Boerwinkle E, Folsom AR, Rose LM, Franco-Cereceda A, Teichert M, Ikram MA, Mosley TH, Bevan S, Dichgans M, Rothwell PM, Sudlow CLM, Hopewell JC, Chambers JC, Saleheen D, Kooner JS, Danesh J, Nelson CP, Erdmann J, Reilly MP, Kathiresan S, Schunkert H, Morange P-E, Ferrucci L, Eriksson JG, Jacobs D, Deary IJ, Soranzo N, Witteman JCM, de Geus EJC, Tracy RP, Hayward C, Koenig W, Cucca F, Jukema JW, Eriksson P, Seshadri S, Markus HS, Watkins H, Samani NJ, Wallaschofski H, Smith NL, Tregouet D, Ridker PM, Tang W, Strachan DP, Hamsten A, O'Donnell CJet al., 2013, Multiethnic Meta-Analysis of Genome-Wide Association Studies in &gt; 100 000 Subjects Identifies 23 FibrinogenAssociated Loci but No Strong Evidence of a Causal Association Between Circulating Fibrinogen and Cardiovascular Disease, CIRCULATION, Vol: 128, Pages: 1310-1324, ISSN: 0009-7322

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• Citations: 113

Wang X, Chua H-X, Chen P, Ong RT-H, Sim X, Zhang W, Takeuchi F, Liu X, Khor C-C, Tay W-T, Cheng C-Y, Suo C, Liu J, Aung T, Chia K-S, Kooner JS, Chambers JC, Wong T-Y, Tai E-S, Kato N, Teo Y-Yet al., 2013, Comparing methods for performing trans-ethnic meta-analysis of genome-wide association studies, HUMAN MOLECULAR GENETICS, Vol: 22, Pages: 2303-2311, ISSN: 0964-6906

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• Citations: 52

den Hoed M, Eijgelsheim M, Esko T, Brundel BJJM, Peal DS, Evans DM, Nolte IM, Segre AV, Holm H, Handsaker RE, Westra H-J, Johnson T, Isaacs A, Yang J, Lundby A, Zhao JH, Kim YJ, Go MJ, Almgren P, Bochud M, Boucher G, Cornelis MC, Gudbjartsson D, Hadley D, van der Harst P, Hayward C, den Heijer M, Igl W, Jackson AU, Kutalik Z, Luan J, Kemp JP, Kristiansson K, Ladenvall C, Lorentzon M, Montasser ME, Njajou OT, O'Reilly PF, Padmanabhan S, Pourcain BS, Rankinen T, Salo P, Tanaka T, Timpson NJ, Vitart V, Waite L, Wheeler W, Zhang W, Draisma HHM, Feitosa MF, Kerr KF, Lind PA, Mihailov E, Onland-Moret NC, Song C, Weedon MN, Xie W, Yengo L, Absher D, Albert CM, Alonso A, Arking DE, de Bakker PIW, Balkau B, Barlassina C, Benaglio P, Bis JC, Bouatia-Naji N, Brage S, Chanock SJ, Chines PS, Chung M, Darbar D, Dina C, Doerr M, Elliott P, Felix SB, Fischer K, Fuchsberger C, de Geus EJC, Goyette P, Gudnason V, Harris TB, Hartikainen A-L, Havulinna AS, Heckbert SR, Hicks AA, Hofman A, Holewijn S, Hoogstra-Berends F, Hottenga J-J, Jensen MK, Johansson A, Junttila J, Kaeaeb S, Kanon B, Ketkar S, Khaw K-T, Knowles JW, Kooner AS, Kors JA, Kumari M, Milani L, Laiho P, Lakatta EG, Langenberg C, Leusink M, Liu Y, Luben RN, Lunetta KL, Lynch SN, Markus MRP, Marques-Vidal P, Leach IM, McArdle WL, McCarroll SA, Medland SE, Miller KA, Montgomery GW, Morrison AC, Mueller-Nurasyid M, Navarro P, Nelis M, O'Connell JR, O'Donnell CJ, Ong KK, Newman AB, Peters A, Polasek O, Pouta A, Pramstaller PP, Psaty BM, Rao DC, Ring SM, Rossin EJ, Rudan D, Sanna S, Scott RA, Sehmi JS, Sharp S, Shin JT, Singleton AB, Smith AV, Soranzo N, Spector TD, Stewart C, Stringham HM, Tarasov KV, Uitterlinden AG, Vandenput L, Hwang S-J, Whitfield JB, Wijmenga C, Wild SH, Willemsen G, Wilson JF, Witteman JCM, Wong A, Wong Q, Jamshidi Y, Zitting P, Boer JMA, Boomsma DI, Borecki IB, van Duijn CM, Ekelund U, Forouhi NG, Froguel P, Hingorani A, Ingelsson E, Kivimaki M, Kronmal RA, Kuh D, Lind L, Martin NG, Oostra BA, Pedersenet al., 2013, Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders, NATURE GENETICS, Vol: 45, Pages: 621-+, ISSN: 1061-4036

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• Citations: 228

Koettgen A, Albrecht E, Teumer A, Vitart V, Krumsiek J, Hundertmark C, Pistis G, Ruggiero D, O'Seaghdha CM, Haller T, Yang Q, Tanaka T, Johnson AD, Kutalik Z, Smith AV, Shi J, Struchalin M, Middelberg RPS, Brown MJ, Gaffo AL, Pirastu N, Li G, Hayward C, Zemunik T, Huffman J, Yengo L, Zhao JH, Demirkan A, Feitosa MF, Liu X, Malerba G, Lopez LM, van der Harst P, Li X, Kleber ME, Hicks AA, Nolte IM, Johansson A, Murgia F, Wild SH, Bakker SJL, Peden JF, Dehghan A, Steri M, Tenesa A, Lagou V, Salo P, Mangino M, Rose LM, Lehtimaki T, Woodward OM, Okada Y, Tin A, Mueller C, Oldmeadow C, Putku M, Czamara D, Kraft P, Frogheri L, Thun GA, Grotevendt A, Gislason GK, Harris TB, Launer LJ, McArdle P, Shuldiner AR, Boerwinkle E, Coresh J, Schmidt H, Schallert M, Martin NG, Montgomery GW, Kubo M, Nakamura Y, Tanaka T, Munroe PB, Samani NJ, Jacobs DR, Liu K, D'Adamo P, Ulivi S, Rotter JI, Psaty BM, Vollenweider P, Waeber G, Campbell S, Devuyst O, Navarro P, Kolcic I, Hastie N, Balkau B, Froguel P, Esko T, Salumets A, Khaw KT, Langenberg C, Wareham NJ, Isaacs A, Kraja A, Zhang Q, Wild PS, Scott RJ, Holliday EG, Org E, Viigimaa M, Bandinelli S, Metter JE, Lupo A, Trabetti E, Sorice R, Doering A, Lattka E, Strauch K, Theis F, Waldenberger M, Wichmann H-E, Davies G, Gow AJ, Bruinenberg M, Stolk RP, Kooner JS, Zhang W, Winkelmann BR, Boehm BO, Lucae S, Penninx BW, Smit JH, Curhan G, Mudgal P, Plenge RM, Portas L, Persico I, Kirin M, Wilson JF, Leach IM, van Gilst WH, Goel A, Ongen H, Hofman A, Rivadeneira F, Uitterlinden AG, Imboden M, von Eckardstein A, Cucca F, Nagaraja R, Piras MG, Nauck M, Schurmann C, Budde K, Ernst F, Farrington SM, Theodoratou E, Prokopenko I, Stumvoll M, Jula A, Perola M, Salomaa V, Shin S-Y, Spector TD, Sala C, Ridker PM, Kaehoenen M, Viikari J, Hengstenberg C, Nelson CP, Meschia JF, Nalls MA, Sharma P, Singleton AB, Kamatani N, Zeller T, Burnier M, Attia J, Laan M, Klopp N, Hillege HL, Kloiber S, Choi H, Pirastu M, Tore S, Probst-Hensch NM, Voelzke H, Gudnasonet al., 2013, Genome-wide association analyses identify 18 new loci associated with serum urate concentrations, NATURE GENETICS, Vol: 45, Pages: 145-154, ISSN: 1061-4036

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• Citations: 561

Deloukas P, Kanoni S, Willenborg C, Farrall M, Assimes TL, Thompson JR, Ingelsson E, Saleheen D, Erdmann J, Goldstein BA, Stirrups K, Koenig IR, Cazier J-B, Johansson A, Hall AS, Lee J-Y, Willer CJ, Chambers JC, Esko T, Folkersen L, Goel A, Grundberg E, Havulinna AS, Ho WK, Hopewell JC, Eriksson N, Kleber ME, Kristiansson K, Lundmark P, Lyytikainen L-P, Rafelt S, Shungin D, Strawbridge RJ, Thorleifsson G, Tikkanen E, Van Zuydam N, Voight BF, Waite LL, Zhang W, Ziegler A, Absher D, Altshuler D, Balmforth AJ, Barroso I, Braund PS, Burgdorf C, Claudi-Boehm S, Cox D, Dimitriou M, Do R, Doney ASF, El Mokhtari N, Eriksson P, Fischer K, Fontanillas P, Franco-Cereceda A, Gigante B, Groop L, Gustafsson S, Hager J, Hallmans G, Han B-G, Hunt SE, Kang HM, Illig T, Kessler T, Knowles JW, Kolovou G, Kuusisto J, Langenberg C, Langford C, Leander K, Lokki M-L, Lundmark A, McCarthy MI, Meisinger C, Melander O, Mihailov E, Maouche S, Morris AD, Mueller-Nurasyid M, Nikus K, Peden JF, Rayner NW, Rasheed A, Rosinger S, Rubin D, Rumpf MP, Schaefer A, Sivananthan M, Song C, Stewart AFR, Tan S-T, Thorgeirsson G, van der Schoot CE, Wagner PJ, Wells GA, Wild PS, Yang T-P, Amouyel P, Arveiler D, Basart H, Boehnke M, Boerwinkle E, Brambilla P, Cambien F, Cupples AL, de Faire U, Dehghan A, Diemert P, Epstein SE, Evans A, Ferrario MM, Ferrieres J, Gauguier D, Go AS, Goodall AH, Gudnason V, Hazen SL, Holm H, Iribarren C, Jang Y, Kahonen M, Kee F, Kim H-S, Klopp N, Koenig W, Kratzer W, Kuulasmaa K, Laakso M, Laaksonen R, Lee J-Y, Lind L, Ouwehand WH, Parish S, Park JE, Pedersen NL, Peters A, Quertermous T, Rader DJ, Salomaa V, Schadt E, Shah SH, Sinisalo J, Stark K, Stefansson K, Tregouet D-A, Virtamo J, Wallentin L, Wareham N, Zimmermann ME, Nieminen MS, Hengstenberg C, Sandhu MS, Pastinen T, Syvanen A-C, Hovingh GK, Dedoussis G, Franks PW, Lehtimaki T, Metspalu A, Zalloua PA, Siegbahn A, Schreiber S, Ripatti S, Blankenberg SS, Perola M, Clarke R, Boehm BO, O'Donnell C, Reilly MP, Maerz W, Collinet al., 2013, Large-scale association analysis identifies new risk loci for coronary artery disease, NATURE GENETICS, Vol: 45, Pages: 25-U52, ISSN: 1061-4036

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• Citations: 959

van der Harst P, Zhang W, Leach IM, Rendon A, Verweij N, Sehmi J, Paul DS, Elling U, Allayee H, Li X, Radhakrishnan A, Tan S-T, Voss K, Weichenberger CX, Albers CA, Al-Hussani A, Asselbergs FW, Ciullo M, Danjou F, Dina C, Esko T, Evans DM, Franke L, Goegele M, Hartiala J, Hersch M, Holm H, Hottenga J-J, Kanoni S, Kleber ME, Lagou V, Langenberg C, Lopez LM, Lyytikainen L-P, Melander O, Murgia F, Nolte IM, O'Reilly PF, Padmanabhan S, Parsa A, Pirastu N, Porcu E, Portas L, Prokopenko I, Ried JS, Shin S-Y, Tang CS, Teumer A, Traglia M, Ulivi S, Westra H-J, Yang J, Zhao JH, Anni F, Abdellaoui A, Attwood A, Balkau B, Bandinelli S, Bastardot F, Benyamin B, Boehm BO, Cookson WO, Das D, de Bakker PIW, de Boer RA, de Geus EJC, de Moor MH, Dimitriou M, Domingues FS, Doering A, Engstrom G, Eyjolfsson GI, Ferrucci L, Fischer K, Galanello R, Garner SF, Genser B, Gibson QD, Girotto G, Gudbjartsson DF, Harris SE, Hartikainen A-L, Hastie CE, Hedblad B, Illig T, Jolley J, Kahonen M, Kema IP, Kemp JP, Liang L, Lloyd-Jones H, Loos RJF, Meacham S, Medland SE, Meisinger C, Memari Y, Mihailov E, Miller K, Moffatt MF, Nauck M, Novatchkova M, Nutile T, Olafsson I, Onundarson PT, Parracciani D, Penninx BW, Perseu L, Piga A, Pistis G, Pouta A, Puc U, Raitakari O, Ring SM, Robino A, Ruggiero D, Ruokonen A, Saint-Pierre A, Sala C, Salumets A, Sambrook J, Schepers H, Schmidt CO, Sillje HHW, Sladek R, Smit JH, Starr JM, Stephens J, Sulem P, Tanaka T, Thorsteinsdottir U, Tragante V, van Gilst WH, van Pelt LJ, van Veldhuisen DJ, Voelker U, Whitfield JB, Willemsen G, Winkelmann BR, Wirnsberger G, Algra A, Cucca F, d'Adamo AP, Danesh J, Deary IJ, Dominiczak AF, Elliott P, Fortina P, Froguel P, Gasparini P, Greinacher A, Hazen SL, Jarvelin M-R, Khaw KT, Lehtimaki T, Maerz W, Martin NG, Metspalu A, Mitchell BD, Montgomery GW, Moore C, Navis G, Pirastu M, Pramstaller PP, Ramirez-Solis R, Schadt E, Scott J, Shuldiner AR, Smith GD, Smith JG, Snieder H, Sorice R, Spector TD, Stefansson K, Stumvoll M, Tanget al., 2012, Seventy-five genetic loci influencing the human red blood cell, NATURE, Vol: 492, Pages: 369-+, ISSN: 0028-0836

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• Citations: 242

Huang J, Sabater-Lleal M, Asselbergs FW, Tregouet D, Shin S-Y, Ding J, Baumert J, Oudot-Mellakh T, Folkersen L, Johnson AD, Smith NL, Williams SM, Ikram MA, Kleber ME, Becker DM, Vinh T, Mychaleckyj JC, Tang W, Yang Q, Sennblad B, Moore JH, Williams FMK, Dehghan A, Silbernagel G, Schrijvers EMC, Smith S, Karakas M, Tofler GH, Silveira A, Navis GJ, Lohman K, Chen M-H, Peters A, Goel A, Hopewell JC, Chambers JC, Saleheen D, Lundmark P, Psaty BM, Strawbridge RJ, Boehm BO, Carter AM, Meisinger C, Peden JF, Bis JC, McKnight B, Ohrvik J, Taylor K, Franzosi MG, Seedorf U, Collins R, Franco-Cereceda A, Syvaenen A-C, Goodall AH, Yanek LR, Cushman M, Mueller-Nurasyid M, Folsom AR, Basu S, Matijevic N, van Gilst WH, Kooner JS, Hofman A, Danesh J, Clarke R, Meigs JB, Kathiresan S, Reilly MP, Klopp N, Harris TB, Winkelmann BR, Grant PJ, Hillege HL, Watkins H, Spector TD, Becker LC, Tracy RP, Maerz W, Uitterlinden AG, Eriksson P, Cambien F, Morange P-E, Koenig W, Soranzo N, van der Harst P, Liu Y, O'Donnell CJ, Hamsten Aet al., 2012, Genome-wide association study for circulating levels of PAI-1 provides novel insights into its regulation, BLOOD, Vol: 120, Pages: 4873-4881, ISSN: 0006-4971

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• Citations: 72

Okada Y, Sim X, Go MJ, Wu J-Y, Gu D, Takeuchi F, Takahashi A, Maeda S, Tsunoda T, Chen P, Lim S-C, Wong T-Y, Liu J, Young TL, Aung T, Seielstad M, Teo Y-Y, Kim YJ, Lee J-Y, Han B-G, Kang D, Chen C-H, Tsai F-J, Chang L-C, Fann S-JC, Mei H, Rao DC, Hixson JE, Chen S, Katsuya T, Isono M, Ogihara T, Chambers JC, Zhang W, Kooner JS, Albrecht E, Yamamoto K, Kubo M, Nakamura Y, Kamatani N, Kato N, He J, Chen Y-T, Cho YS, Tai E-S, Tanaka Tet al., 2012, Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations, NATURE GENETICS, Vol: 44, Pages: 904-+, ISSN: 1061-4036

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• Citations: 220

Sarwar N, Butterworth AS, Freitag DF, Gregson J, Willeit P, Gorman DN, Gao P, Saleheen D, Rendon A, Nelson CP, Braund PS, Hall AS, Chasman DI, Tybjaerg-Hansen A, Chambers JC, Benjamin EJ, Franks PW, Clarke R, Wilde AAM, Trip MD, Steri M, Witteman JCM, Qi L, van der Schoot CE, de Faire U, Erdmann J, Stringham HM, Koenig W, Rader DJ, Melzer D, Reich D, Psaty BM, Kleber ME, Panagiotakos DB, Willeit J, Wennberg P, Woodward M, Adamovic S, Rimm EB, Meade TW, Gillum RF, Shaffer JA, Hofman A, Onat A, Sundstrom J, Wassertheil-Smoller S, Mellstrom D, Gallacher J, Cushman M, Tracy RP, Kauhanen J, Karlsson M, Salonen JT, Wilhelmsen L, Amouyel P, Cantin B, Best LG, Ben-Shlomo Y, Manson JE, Davey-Smith G, de Bakker PIW, O'Donnell CJ, Wilson JF, Wilson AG, Assimes TL, Jansson J-O, Ohlsson C, Tivesten A, Ljunggren O, Reilly MP, Hamsten A, Ingelsson E, Cambien F, Hung J, Thomas GN, Boehnke M, Schunkert H, Asselbergs FW, Kastelein JJP, Gudnason V, Salomaa V, Harris TB, Kooner JS, Allin KH, Nordestgaard BG, Hopewell JC, Goodall AH, Ridker PM, Holm H, Watkins H, Ouwehand WH, Samani NJ, Kaptoge S, Di Angelantonio E, Harari O, Danesh Jet al., 2012, Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies, LANCET, Vol: 379, Pages: 1205-1213, ISSN: 0140-6736

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• Citations: 580

Dastani Z, Hivert M-F, Timpson N, Perry JRB, Yuan X, Scott RA, Henneman P, Heid IM, Kizer JR, Lyytikainen L-P, Fuchsberger C, Tanaka T, Morris AP, Small K, Isaacs A, Beekman M, Coassin S, Lohman K, Qi L, Kanoni S, Pankow JS, Uh H-W, Wu Y, Bidulescu A, Rasmussen-Torvik LJ, Greenwood CMT, Ladouceur M, Grimsby J, Manning AK, Liu C-T, Kooner J, Mooser VE, Vollenweider P, Kapur KA, Chambers J, Wareham NJ, Langenberg C, Frants R, Willems-vanDijk K, Oostra BA, Willems SM, Lamina C, Winkler TW, Psaty BM, Tracy RP, Brody J, Chen I, Viikari J, Kahonen M, Pramstaller PP, Evans DM, St Pourcain B, Sattar N, Wood AR, Bandinelli S, Carlson OD, Egan JM, Bohringer S, van Heemst D, Kedenko L, Kristiansson K, Nuotio M-L, Loo B-M, Harris T, Garcia M, Kanaya A, Haun M, Klopp N, Wichmann H-E, Deloukas P, Katsareli E, Couper DJ, Duncan BB, Kloppenburg M, Adair LS, Borja JB, Wilson JG, Musani S, Guo X, Johnson T, Semple R, Teslovich TM, Allison MA, Redline S, Buxbaum SG, Mohlke KL, Meulenbelt I, Ballantyne CM, Dedoussis GV, Hu FB, Liu Y, Paulweber B, Spector TD, Slagboom PE, Ferrucci L, Jula A, Perola M, Raitakari O, Florez JC, Salomaa V, Eriksson JG, Frayling TM, Hicks AA, Lehtimaki T, Smith GD, Siscovick DS, Kronenberg F, van Duijn C, Loos RJF, Waterworth DM, Meigs JB, Dupuis J, Richards JBet al., 2012, Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits: A Multi-Ethnic Meta-Analysis of 45,891 Individuals, PLOS Genetics, Vol: 8, ISSN: 1553-7390

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inverselyassociated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wideassociation studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. Weidentified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.561028–1.2610243). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, andN = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samplesrevealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations afteraccounting for multiple testing (p,361024). We next developed a multi-SNP genotypic risk score to test the associationof adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This riskscore was associated with increased risk of T2D (p = 4.361023, n = 22,044), increased triglycerides (p = 2.6610214,n = 93,440), increased waist-to-hip ratio (p = 1.861025, n = 77,167), increased glucose two hours post oral glucosetolerance testing (p = 4.461023, n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDLcholesterolconcentrations (p = 4.5610213, n = 96,748) and decreased BMI (p = 1.461024, n = 121,335). These findingsidentify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers ofinsulin resistance.

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Gieger C, Radhakrishnan A, Cvejic A, Tang W, Porcu E, Pistis G, Serbanovic-Canic J, Elling U, Goodall AH, Labrune Y, Lopez LM, Maegi R, Meacham S, Okada Y, Pirastu N, Sorice R, Teumer A, Voss K, Zhang W, Ramirez-Solis R, Bis JC, Ellinghaus D, Goegele M, Hottenga J-J, Langenberg C, Kovacs P, O'Reilly PF, Shin S-Y, Esko T, Hartiala J, Kanoni S, Murgia F, Parsa A, Stephens J, van der Harst P, van der Schoot CE, Allayee H, Attwood A, Balkau B, Bastardot F, Basu S, Baumeister SE, Biino G, Bomba L, Bonnefond A, Cambien F, Chambers JC, Cucca F, D'Adamo P, Davies G, de Boer RA, de Geus EJC, Doering A, Elliott P, Erdmann J, Evans DM, Falchi M, Feng W, Folsom AR, Frazer IH, Gibson QD, Glazer NL, Hammond C, Hartikainen A-L, Heckbert SR, Hengstenberg C, Hersch M, Illig T, Loos RJF, Jolley J, Khaw KT, Kuehnel B, Kyrtsonis M-C, Lagou V, Lloyd-Jones H, Lumley T, Mangino M, Maschio A, Leach IM, McKnight B, Memari Y, Mitchell BD, Montgomery GW, Nakamura Y, Nauck M, Navis G, Noethlings U, Nolte IM, Porteous DJ, Pouta A, Pramstaller PP, Pullat J, Ring SM, Rotter JI, Ruggiero D, Ruokonen A, Sala C, Samani NJ, Sambrook J, Schlessinger D, Schreiber S, Schunkert H, Scott J, Smith NL, Snieder H, Starr JM, Stumvoll M, Takahashi A, Tang WHW, Taylor K, Tenesa A, Thein SL, Toenjes A, Uda M, Ulivi S, van Veldhuisen DJ, Visscher PM, Voelker U, Wichmann H-E, Wiggins KL, Willemsen G, Yang T-P, Zhao JH, Zitting P, Bradley JR, Dedoussis GV, Gasparini P, Hazen SL, Metspalu A, Pirastu M, Shuldiner AR, van Pelt LJ, Zwaginga J-J, Boomsma DI, Deary IJ, Franke A, Froguel P, Ganesh SK, Jarvelin M-R, Martin NG, Meisinger C, Psaty BM, Spector TD, Wareham NJ, Akkerman J-WN, Ciullo M, Deloukas P, Greinacher A, Jupe S, Kamatani N, Khadake J, Kooner JS, Penninger J, Prokopenko I, Stemple D, Toniolo D, Wernisch L, Sanna S, Hicks AA, Rendon A, Ferreira MA, Ouwehand WH, Soranzo Net al., 2011, New gene functions in megakaryopoiesis and platelet formation, NATURE, Vol: 480, Pages: 201-208, ISSN: 0028-0836

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• Citations: 310

Chambers JC, Zhang W, Sehmi J, Li X, Wass MN, Van der Harst P, Holm H, Sanna S, Kavousi M, Baumeister SE, Coin LJ, Deng G, Gieger C, Heard-Costa NL, Hottenga J-J, Kuehnel B, Kumar V, Lagou V, Liang L, Luan J, Vidal PM, Leach IM, O'Reilly PF, Peden JF, Rahmioglu N, Soininen P, Speliotes EK, Yuan X, Thorleifsson G, Alizadeh BZ, Atwood LD, Borecki IB, Brown MJ, Charoen P, Cucca F, Das D, de Geus EJC, Dixon AL, Doering A, Ehret G, Eyjolfsson GI, Farrall M, Forouhi NG, Friedrich N, Goessling W, Gudbjartsson DF, Harris TB, Hartikainen A-L, Heath S, Hirschfield GM, Hofman A, Homuth G, Hyppoenen E, Janssen HLA, Johnson T, Kangas AJ, Kema IP, Kuehn JP, Lai S, Lathrop M, Lerch MM, Li Y, Liang TJ, Lin J-P, Loos RJF, Martin NG, Moffatt MF, Montgomery GW, Munroe PB, Musunuru K, Nakamura Y, O'Donnell CJ, Olafsson I, Penninx BW, Pouta A, Prins BP, Prokopenko I, Puls R, Ruokonen A, Savolainen MJ, Schlessinger D, Schouten JNL, Seedorf U, Sen-Chowdhry S, Siminovitch KA, Smit JH, Spector TD, Tan W, Teslovich TM, Tukiainen T, Uitterlinden AG, Van der Klauw MM, Vasan RS, Wallace C, Wallaschofski H, Wichmann H-E, Willemsen G, Wuertz P, Xu C, Yerges-Armstrong LM, Abecasis GR, Ahmadi KR, Boomsma DI, Caulfield M, Cookson WO, van Duijn CM, Froguel P, Matsuda K, McCarthy MI, Meisinger C, Mooser V, Pietilainen KH, Schumann G, Snieder H, Sternberg MJE, Stolk RP, Thomas HC, Thorsteinsdottir U, Uda M, Waeber G, Wareham NJ, Waterworth DM, Watkins H, Whitfield JB, Witteman JCM, Wolffenbuttel BHR, Fox CS, Ala-Korpela M, Stefansson K, Vollenweider P, Voelzke H, Schadt EE, Scott J, Jarvelin M-R, Elliott P, Kooner JSet al., 2011, Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma, NATURE GENETICS, Vol: 43, Pages: 1131-1138, ISSN: 1061-4036

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• Citations: 409

Ehret GB, Munroe PB, Rice KM, Bochud M, Johnson AD, Chasman DI, Smith AV, Tobin MD, Verwoert GC, Hwang S-J, Pihur V, Vollenweider P, O'Reilly PF, Amin N, Bragg-Gresham JL, Teumer A, Glazer NL, Launer L, Zhao JH, Aulchenko Y, Heath S, Sober S, Parsa A, Luan J, Arora P, Dehghan A, Zhang F, Lucas G, Hicks AA, Jackson AU, Peden JF, Tanaka T, Wild SH, Rudan I, Igl W, Milaneschi Y, Parker AN, Fava C, Chambers JC, Fox ER, Kumari M, Go MJ, van der Harst P, Kao WHL, Sjogren M, Vinay DG, Alexander M, Tabara Y, Shaw-Hawkins S, Whincup PH, Liu Y, Shi G, Kuusisto J, Tayo B, Seielstad M, Sim X, Khanh-Dung HN, Lehtimaki T, Matullo G, Wu Y, Gaunt TR, Onland-Moret NC, Cooper MN, Platou CGP, Org E, Hardy R, Dahgam S, Palmen J, Vitart V, Braund PS, Kuznetsova T, Uiterwaal CSPM, Adeyemo A, Palmas W, Campbell H, Ludwig B, Tomaszewski M, Tzoulaki I, Palmer ND, Aspelund T, Garcia M, Chang Y-PC, O'Connell JR, Steinle NI, Grobbee DE, Arking DE, Kardia SL, Morrison AC, Hernandez D, Najjar S, McArdle WL, Hadley D, Brown MJ, Connell JM, Hingorani AD, Day INM, Lawlor DA, Beilby JP, Lawrence RW, Clarke R, Hopewell JC, Ongen H, Dreisbach AW, Li Y, Young JH, Bis JC, Kahonen M, Viikari J, Adair LS, Lee NR, Chen M-H, Olden M, Pattaro C, Bolton JAH, Koettgen A, Bergmann S, Mooser V, Chaturvedi N, Frayling TM, Islam M, Jafar TH, Erdmann J, Kulkarni SR, Bornstein SR, Graessler J, Groop L, Voight BF, Kettunen J, Howard P, Taylor A, Guarrera S, Ricceri F, Emilsson V, Plump A, Barroso IS, Khaw K-T, Weder AB, Hunt SC, Sun YV, Bergman RN, Collins FS, Bonnycastle LL, Scott LJ, Stringham HM, Peltonen L, Perola M, Vartiainen E, Brand S-M, Staessen JA, Wang TJ, Burton PR, Artigas MS, Dong Y, Snieder H, Wang X, Zhu H, Lohman KK, Rudock ME, Heckbert SR, Smith NL, Wiggins KL, Doumatey A, Shriner D, Veldre G, Viigimaa M, Kinra S, Prabhakaran D, Tripathy V, Langefeld CD, Rosengren A, Thelle DS, Corsi AM, Singleton A, Forrester T, Hilton G, McKenzie CA, Salako T, Iwai N, Kita Y, Ogihara T, Ohkubo T, Okamura T, Ueshimet al., 2011, Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk, NATURE, Vol: 478, Pages: 103-109, ISSN: 0028-0836

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• Citations: 1509

Kooner JS, Saleheen D, Sim X, Sehmi J, Zhang W, Frossard P, Been LF, Chia K-S, Dimas AS, Hassanali N, Jafar T, Jowett JBM, Li X, Radha V, Rees SD, Takeuchi F, Young R, Aung T, Basit A, Chidambaram M, Das D, Grundberg E, Hedman AK, Hydrie ZI, Islam M, Khor C-C, Kowlessur S, Kristensen MM, Liju S, Lim W-Y, Matthews DR, Liu J, Morris AP, Nica AC, Pinidiyapathirage JM, Prokopenko I, Rasheed A, Samuel M, Shah N, Shera AS, Small KS, Suo C, Wickremasinghe AR, Wong TY, Yang M, Zhang F, Abecasis GR, Barnett AH, Caulfield M, Deloukas P, Frayling TM, Froguel P, Kato N, Katulanda P, Kelly MA, Liang J, Mohan V, Sanghera DK, Scott J, Seielstad M, Zimmet PZ, Elliott P, Teo YY, McCarthy MI, Danesh J, Tai ES, Chambers JCet al., 2011, Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci, NATURE GENETICS, Vol: 43, Pages: 984-U94, ISSN: 1061-4036

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• Citations: 398

Wain LV, Verwoert GC, O'Reilly PF, Shi G, Johnson T, Johnson AD, Bochud M, Rice KM, Henneman P, Smith AV, Ehret GB, Amin N, Larson MG, Mooser V, Hadley D, Doerr M, Bis JC, Aspelund T, Esko T, Janssens ACJW, Zhao JH, Heath S, Laan M, Fu J, Pistis G, Luan J, Arora P, Lucas G, Pirastu N, Pichler I, Jackson AU, Webster RJ, Zhang F, Peden JF, Schmidt H, Tanaka T, Campbell H, Igl W, Milaneschi Y, Hottenga J-J, Vitart V, Chasman DI, Trompet S, Bragg-Gresham JL, Alizadeh BZ, Chambers JC, Guo X, Lehtimaki T, Kuehnel B, Lopez LM, Polasek O, Boban M, Nelson CP, Morrison AC, Pihur V, Ganesh SK, Hofman A, Kundu S, Mattace-Raso FUS, Rivadeneira F, Sijbrands EJG, Uitterlinden AG, Hwang S-J, Vasan RS, Wang TJ, Bergmann S, Vollenweider P, Waeber G, Laitinen J, Pouta A, Zitting P, McArdle WL, Kroemer HK, Voelker U, Voelzke H, Glazer NL, Taylor KD, Harris TB, Alavere H, Haller T, Keis A, Tammesoo M-L, Aulchenko Y, Barroso I, Khaw K-T, Galan P, Hercberg S, Lathrop M, Eyheramendy S, Org E, Sober S, Lu X, Nolte IM, Penninx BW, Corre T, Masciullo C, Sala C, Groop L, Voight BF, Melander O, O'Donnell CJ, Salomaa V, d'Adamo AP, Fabretto A, Faletra F, Ulivi S, Del Greco FM, Facheris M, Collins FS, Bergman RN, Beilby JP, Hung J, Musk AW, Mangino M, Shin S-Y, Soranzo N, Watkins H, Goel A, Hamsten A, Gider P, Loitfelder M, Zeginigg M, Hernandez D, Najjar SS, Navarro P, Wild SH, Corsi AM, Singleton A, de Geus EJC, Willemsen G, Parker AN, Rose LM, Buckley B, Stott D, Orru M, Uda M, van der Klauw MM, Zhang W, Li X, Scott J, Chen Y-DI, Burke GL, Kahonen M, Viikari J, Doering A, Meitinger T, Davies G, Starr JM, Emilsson V, Plump A, Lindeman JH, 't Hoen PAC, Koenig IR, Felix JF, Clarke R, Hopewell JC, Ongen H, Breteler M, Debette S, DeStefano AL, Fornage M, Mitchell GF, Smith NL, Holm H, Stefansson K, Thorleifsson G, Thorsteinsdottir U, Samani NJ, Preuss M, Rudan I, Hayward C, Deary IJ, Wichmann H-E, Raitakari OT, Palmas W, Kooner JS, Stolk RP, Jukema JW, Wright AF, Boomsma DI, Bandinelli S, Gyllensteet al., 2011, Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure, NATURE GENETICS, Vol: 43, Pages: 1005-U122, ISSN: 1061-4036

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans1,2,3. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10−8 to P = 2.3 × 10−13) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.

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Das D, Sehmi J, Ahmed N, Kooner A, Miller K, Scott J, Elliot P, Chambers JC, Kooner JSet al., 2011, Comparison of known genetic variants to coronary heart disease risk between Indian Asians and Europeans, EUROPEAN HEART JOURNAL, Vol: 32, Pages: 652-652, ISSN: 0195-668X

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Kilpelainen TO, Zillikens MC, Stancakova A, Finucane FM, Ried JS, Langenberg C, Zhang W, Beckmann JS, Luan J, Vandenput L, Styrkarsdottir U, Zhou Y, Smith AV, Zhao J-H, Amin N, Vedantam S, Shin S-Y, Haritunians T, Fu M, Feitosa MF, Kumari M, Halldorsson BV, Tikkanen E, Mangino M, Hayward C, Song C, Arnold AM, Aulchenko YS, Oostra BA, Campbell H, Cupples LA, Davis KE, Doering A, Eiriksdottir G, Estrada K, Manuel Fernandez-Real J, Garcia M, Gieger C, Glazer NL, Guiducci C, Hofman A, Humphries SE, Isomaa B, Jacobs LC, Jula A, Karasik D, Karlsson MK, Khaw K-T, Kim LJ, Kivimaeki M, Klopp N, Kuehnel B, Kuusisto J, Liu Y, Ljunggren O, Lorentzon M, Luben RN, McKnight B, Mellstrom D, Mitchell BD, Mooser V, Maria Moreno J, Mannisto S, O'Connell JR, Pascoe L, Peltonen L, Peral B, Perola M, Psaty BM, Salomaa V, Savage DB, Semple RK, Skaric-Juric T, Sigurdsson G, Song KS, Spector TD, Syvanen A-C, Talmud PJ, Thorleifsson G, Thorsteinsdottir U, Uitterlinden AG, van Duijn CM, Vidal-Puig A, Wild SH, Wright AF, Clegg DJ, Schadt E, Wilson JF, Rudan I, Ripatti S, Borecki IB, Shuldiner AR, Ingelsson E, Jansson J-O, Kaplan RC, Gudnason V, Harris TB, Groop L, Kiel DP, Rivadeneira F, Walker M, Barroso I, Vollenweider P, Waeber G, Chambers JC, Kooner JS, Soranzo N, Hirschhorn JN, Stefansson K, Wichmann H-E, Ohlsson C, O'Rahilly S, Wareham NJ, Speliotes EK, Fox CS, Laakso M, Loos RJFet al., 2011, Genetic variation near <i>IRS1</i> associates with reduced adiposity and an impaired metabolic profile, NATURE GENETICS, Vol: 43, Pages: 753-U58, ISSN: 1061-4036

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• Citations: 229

Sehmi J, Saleheen D, Yeo IY, Zhang W, Das D, Mccarthy MI, Tai ES, Danesh J, Kooner JS, Chambers JCet al., 2011, A genome-wide association study in Indian Asians identifies five novel genetic variants for type-2 diabetes, EUROPEAN HEART JOURNAL, Vol: 32, Pages: 357-357, ISSN: 0195-668X

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Sehmi J, Yeo IY, Salaheen S, Zhang W, Das D, Danesh J, Tai ES, Mccarthy MI, Chambers JC, Kooner JSet al., 2011, Contribution of known genetic variants to increased risk of type-2 diabetes in Indian Asians, EUROPEAN HEART JOURNAL, Vol: 32, Pages: 673-673, ISSN: 0195-668X

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Peden JF, Hopewell JC, Saleheen D, Chambers JC, Hager J, Soranzo N, Collins R, Danesh J, Elliott P, Farrall M, Stirrups K, Zhang W, Hamsten A, Parish S, Lathrop M, Watkins H, Clarke R, Deloukas P, Kooner JS, Goel A, Ongen H, Strawbridge RJ, Heath S, Malarstig A, Helgadottir A, Ohrvik J, Murtaza M, Potter S, Hunt SE, Delepine M, Jalilzadeh S, Axelsson T, Syvanen A-C, Gwilliam R, Bumpstead S, Gray E, Edkins S, Folkersen L, Kyriakou T, Franco-Cereceda A, Gabrielsen A, Seedorf U, Eriksson P, Offer A, Bowman L, Sleight P, Armitage J, Peto R, Abecasis G, Ahmed N, Caulfield M, Donnelly P, Froguel P, Kooner AS, McCarthy MI, Samani NJ, Scott J, Sehmi J, Silveira A, Hellenius M-L, van't Hooft FM, Olsson G, Rust S, Assmann G, Barlera S, Tognoni G, Franzosi MG, Linksted P, Green FR, Rasheed A, Zaidi M, Shah N, Samuel M, Mallick NH, Azhar M, Zaman KS, Samad A, Ishaq M, Gardezi AR, Memon F-U-R, Frossard PM, Spector T, Peltonen L, Nieminen MS, Sinisalo J, Salomaa V, Ripatti S, Bennett D, Leander K, Gigante B, de Faire U, Pietri S, Gori F, Marchioli R, Sivapalaratnam S, Kastelein JJP, Trip MD, Theodoraki EV, Dedoussis GV, Engert JC, Yusuf S, Anand SSet al., 2011, A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease, NATURE GENETICS, Vol: 43, Pages: 339-U89, ISSN: 1061-4036

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• Citations: 532

Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki M, Pirruccello JP, Ripatti S, Chasman DI, Willer CJ, Johansen CT, Fouchier SW, Isaacs A, Peloso GM, Barbalic M, Ricketts SL, Bis JC, Aulchenko YS, Thorleifsson G, Feitosa MF, Chambers J, Orho-Melander M, Melander O, Johnson T, Li X, Guo X, Li M, Cho YS, Go MJ, Kim YJ, Lee J-Y, Park T, Kim K, Sim X, Ong RT-H, Croteau-Chonka DC, Lange LA, Smith JD, Song K, Zhao JH, Yuan X, Luan J, Lamina C, Ziegler A, Zhang W, Zee RYL, Wright AF, Witteman JCM, Wilson JF, Willemsen G, Wichmann H-E, Whitfield JB, Waterworth DM, Wareham NJ, Waeber G, Vollenweider P, Voight BF, Vitart V, Uitterlinden AG, Uda M, Tuomilehto J, Thompson JR, Tanaka T, Surakka I, Stringham HM, Spector TD, Soranzo N, Smit JH, Sinisalo J, Silander K, Sijbrands EJG, Scuteri A, Scott J, Schlessinger D, Sanna S, Salomaa V, Saharinen J, Sabatti C, Ruokonen A, Rudan I, Rose LM, Roberts R, Rieder M, Psaty BM, Pramstaller PP, Pichler I, Perola M, Penninx BWJH, Pedersen NL, Pattaro C, Parker AN, Pare G, Oostra BA, O'Donnell CJ, Nieminen MS, Nickerson DA, Montgomery GW, Meitinger T, McPherson R, McCarthy MI, McArdle W, Masson D, Martin NG, Marroni F, Mangino M, Magnusson PKE, Lucas G, Luben R, Loos RJF, Lokki M-L, Lettre G, Langenberg C, Launer LJ, Lakatta EG, Laaksonen R, Kyvik KO, Kronenberg F, Koenig IR, Khaw K-T, Kaprio J, Kaplan LM, Johansson A, Jarvelin M-R, Janssens ACJW, Ingelsson E, Igi W, Hovingh GK, Hottenga J-J, Hofman A, Hicks AA, Hengstenberg C, Heid IM, Hayward C, Havulinna AS, Hastie ND, Harris TB, Haritunians T, Hall AS, Gyllensten U, Guiducci C, Groop LC, Gonzalez E, Gieger C, Freimer NB, Ferrucci L, Erdmann J, Elliott P, Ejebe KG, Doering A, Dominiczak AF, Demissie S, Deloukas P, de Geus EJC, de Faire U, Crawford G, Collins FS, Chen Y-DI, Caulfield MJ, Campbell H, Burtt NP, Bonnycastle LL, Boomsma DI, Boekholdt SM, Bergman RN, Barroso I, Bandinelli S, Ballantyne CM, Assimes TL, Quertermous T, Altshuler D, Seielstad M, Wong TY, Tai Eet al., 2010, Biological, clinical and population relevance of 95 loci for blood lipids, Nature, Vol: 466, Pages: 707-713, ISSN: 0028-0836

Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 × 10−8), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes—GALNT2, PPP1R3B and TTC39B—with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.

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Kapur K, Johnson T, Beckmann ND, Sehmi J, Tanaka T, Kutalik Z, Styrkarsdottir U, Zhang W, Marek D, Gudbjartsson DF, Milaneschi Y, Holm H, DiIorio A, Waterworth D, Li Y, Singleton AB, Bjornsdottir US, Sigurdsson G, Hernandez DG, DeSilva R, Elliott P, Eyjolfsson GI, Guralnik JM, Scott J, Thorsteinsdottir U, Bandinelli S, Chambers J, Stefansson K, Waeber G, Ferrucci L, Kooner JS, Mooser V, Vollenweider P, Beckmann JS, Bochud M, Bergmann Set al., 2010, Genome-Wide Meta-Analysis for Serum Calcium Identifies Significantly Associated SNPs near the Calcium-Sensing Receptor (CASR) Gene, PLOS Genetics, Vol: 6, ISSN: 1553-7390

Calcium has a pivotal role in biological functions, and serum calcium levels have been associated with numerous disordersof bone and mineral metabolism, as well as with cardiovascular mortality. Here we report results from a genome-wideassociation study of serum calcium, integrating data from four independent cohorts including a total of 12,865 individualsof European and Indian Asian descent. Our meta-analysis shows that serum calcium is associated with SNPs in or near thecalcium-sensing receptor (CASR) gene on 3q13. The top hit with a p-value of 6.3610-37 is rs1801725, a missense variant,explaining 1.26% of the variance in serum calcium. This SNP had the strongest association in individuals of Europeandescent, while for individuals of Indian Asian descent the top hit was rs17251221 (p = 1.1610-21), a SNP in strong linkagedisequilibrium with rs1801725. The strongest locus in CASR was shown to replicate in an independent Icelandic cohort of4,126 individuals (p = 1.02610-4). This genome-wide meta-analysis shows that common CASR variants modulate serumcalcium levels in the adult general population, which confirms previous results in some candidate gene studies of the CASRlocus. This study highlights the key role of CASR in calcium regulation.

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Gaemperli O, Liga R, Spyrou N, Rosen SD, Foale R, Kooner JS, Rimoldi OE, Camici PGet al., 2010, Myocardial β-adrenoceptor down-regulation early after infarction is associated with long-term incidence of congestive heart failure, EUROPEAN HEART JOURNAL, Vol: 31, Pages: 1722-1729, ISSN: 0195-668X

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Chahal N, Lim TK, Melderis S, Jain P, Chambers JC, Kooner JS, Senior Ret al., 2010, INCREASED CAROTID ARTERY PLAQUE BURDEN IS ASSOCIATED WITH REDUCED SYSTOLIC LEFT VENTRICULAR FUNCTION AND INCREASED FILLING PRESSURE IN ASYMPTOMATIC INDIVIDUALS, Annual Conference and Exhibition of the British-Cardiovascular-Society, Publisher: B M J PUBLISHING GROUP, Pages: A65-A66, ISSN: 1355-6037

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Chambers JC, Zhang W, Lord GM, van der Harst P, Lawlor DA, Sehmi JS, Gale DP, Wass MN, Ahmadi KR, Bakker SJL, Beckmann J, Bilo HJG, Bochud M, Brown MJ, Caulfield MJ, Connell JMC, Cook HT, Cotlarciuc I, Smith GD, de Silva R, Deng G, Devuyst O, Dikkeschei LD, Dimkovic N, Dockrell M, Dominiczak A, Ebrahim S, Eggermann T, Farrall M, Ferrucci L, Floege J, Forouhi NG, Gansevoort RT, Han X, Hedblad B, van der Heide JJH, Hepkema BG, Hernandez-Fuentes M, Hypponen E, Johnson T, de Jong PE, Kleefstra N, Lagou V, Lapsley M, Li Y, Loos RJF, Luan J, Luttropp K, Marechal C, Melander O, Munroe PB, Nordfors L, Parsa A, Peltonen L, Penninx BW, Perucha E, Pouta A, Prokopenko I, Roderick PJ, Ruokonen A, Samani NJ, Sanna S, Schalling M, Schlessinger D, Schlieper G, Seelen MAJ, Shuldiner AR, Sjogren M, Smit JH, Snieder H, Soranzo N, Spector TD, Stenvinkel P, Sternberg MJE, Swaminathan R, Tanaka T, Ubink-Veltmaat LJ, Uda M, Vollenweider P, Wallace C, Waterworth D, Zerres K, Waeber G, Wareham NJ, Maxwell PH, McCarthy MI, Jarvelin M-R, Mooser V, Abecasis GR, Lightstone L, Scott J, Navis G, Elliott P, Kooner JSet al., 2010, Genetic loci influencing kidney function and chronic kidney disease, NATURE GENETICS, Vol: 42, Pages: 373-375, ISSN: 1061-4036

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• Citations: 215