ProfessorAbbasDehghan

Desikan RS, Schork AJ, Wang Y, Thompson WK, Dehghan A, Ridker PM, Chasman DI, McEvoy LK, Holland D, Chen C-H, Karow DS, Brewer JB, Hess CP, Williams J, Sims R, O'Donovan MC, Choi SH, Bis JC, Ikram MA, Gudnason V, DeStefano AL, van der Lee SJ, Psaty BM, van Duijn CM, Launer L, Seshadri S, Pericak-Vance MA, Mayeux R, Haines JL, Farrer LA, Hardy J, Ulstein ID, Aarsland D, Fladby T, White LR, Sando SB, Rongve A, Witoelar A, Djurovic S, Hyman BT, Snaedal J, Steinberg S, Stefansson H, Stefansson K, Schellenberg GD, Andreassen OA, Dale AMet al., 2015, Polygenic Overlap Between C-Reactive Protein, Plasma Lipids, and Alzheimer Disease, CIRCULATION, Vol: 131, Pages: 2061-2069, ISSN: 0009-7322

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• Citations: 99

Muka T, Kiefte-de Jong JC, Hofman A, Dehghan A, Rivadeneira F, Franco OHet al., 2015, Polyunsaturated Fatty Acids and Serum C-Reactive Protein The Rotterdam Study, AMERICAN JOURNAL OF EPIDEMIOLOGY, Vol: 181, Pages: 846-856, ISSN: 0002-9262

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• Citations: 36

Ghanbari M, Franco OH, de Looper HWJ, Hofman A, Erkeland SJ, Dehghan Aet al., 2015, Genetic Variations in MicroRNA-Binding Sites Affect MicroRNA-Mediated Regulation of Several Genes Associated With Cardio-metabolic Phenotypes, CIRCULATION-CARDIOVASCULAR GENETICS, Vol: 8, Pages: 473-486, ISSN: 1942-325X

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• Citations: 54

Chaker L, Baumgartner C, den Elzen WPJ, Ikram MA, Blum MR, Collet T-H, Bakker SJL, Dehghan A, Drechsler C, Luben RN, Hofman A, Portegies MLP, Medici M, Iervasi G, Stott DJ, Ford I, Bremner A, Wanner C, Ferrucci L, Newman AB, Dullaart RP, Sgarbi JA, Ceresini G, Maciel RMB, Westendorp RG, Jukema JW, Imaizumi M, Franklyn JA, Bauer DC, Walsh JP, Razvi S, Khaw K-T, Cappola AR, Voelzke H, Franco OH, Gussekloo J, Rodondi N, Peeters RPet al., 2015, Subclinical Hypothyroidism and the Risk of Stroke Events and Fatal Stroke: An Individual Participant Data Analysis, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 100, Pages: 2181-2191, ISSN: 0021-972X

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• Citations: 121

Steenaard RV, Ligthart S, Stolk L, Peters MJ, van Meurs JB, Uitterlinden AG, Hofman A, Franco OH, Dehghan Aet al., 2015, Tobacco smoking is associated with methylation of genes related to coronary artery disease, CLINICAL EPIGENETICS, Vol: 7, ISSN: 1868-7075

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• Citations: 51

Fall T, Hagg S, Ploner A, Maegi R, Fischer K, Draisma HHM, Sarin A-P, Benyamin B, Ladenvall C, Akerlund M, Kals M, Esko T, Nelson CP, Kaakinen M, Huikari V, Mangino M, Meirhaeghe A, Kristiansson K, Nuotio M-L, Kobl M, Grallert H, Dehghan A, Kuningas M, de Vries PS, de Bruijn RFAG, Willems SM, Heikkila K, Silventoinen K, Pietilainen KH, Legry V, Giedraitis V, Goumidi L, Syvanen A-C, Strauch K, Koenig W, Lichtner P, Herder C, Palotie A, Menni C, Uitterlinden AG, Kuulasmaa K, Havulinna AS, Moreno LA, Gonzalez-Gross M, Evans A, Tregouet D-A, Yarnell JWG, Virtamo J, Ferrieres J, Veronesi G, Perola M, Arveiler D, Brambilla P, Lind L, Kaprio J, Hofman A, Stricker BH, van Duijn CM, Ikram MA, Franco OH, Cottel D, Dallongeville J, Hall AS, Jula A, Tobin MD, Penninx BW, Peters A, Gieger C, Samani NJ, Montgomery GW, Whiteld JB, Martin NG, Groop L, Spector TD, Magnusson PK, Amouyel P, Boomsma DI, Nilsson PM, Jarvelin M-R, Lyssenko V, Metspalu A, Strachan DP, Salomaa V, Ripatti S, Pedersen NL, Prokopenko I, McCarthy MI, Ingelsson Eet al., 2015, Age- and Sex-Specific Causal Effects of Adiposity on Cardiovascular Risk Factors, DIABETES, Vol: 64, Pages: 1841-1852, ISSN: 0012-1797

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• Citations: 52

Gorski M, Tin A, Garnaas M, McMahon GM, Chu AY, Tayo BO, Pattaro C, Teumer A, Chasman DI, Chalmers J, Hamet P, Tremblay J, Woodward M, Aspelund T, Eiriksdottir G, Gudnason V, Harris TB, Launer LJ, Smith AV, Mitchell BD, O'Connell JR, Shuldiner AR, Coresh J, Li M, Freudenberger P, Hofer E, Schmidt H, Schmidt R, Holliday EG, Mitchell P, Wang JJ, de Boer IH, Li G, Siscovick DS, Kutalik Z, Corre T, Vollenweider P, Waeber G, Gupta J, Kanetsky PA, Hwang S-J, Olden M, Yang Q, de Andrade M, Atkinson EJ, Kardia SLR, Turner ST, Stafford JM, Ding J, Liu Y, Barlassina C, Cusi D, Salvi E, Staessen JA, Ridker PM, Grallert H, Meisinger C, Mueller-Nurasyid M, Kraemer BK, Kramer H, Rosas SE, Nolte IM, Penninx BW, Snieder H, Del Greco MF, Franke A, Noethlings U, Lieb W, Bakker SJL, Gansevoort RT, van der Harst P, Dehghan A, Franco OH, Hofman A, Rivadeneira F, Sedaghat S, Uitterlinden AG, Coassin S, Haun M, Kollerits B, Kronenberg F, Paulweber B, Aumann N, Endlich K, Pietzner M, Voelker U, Rettig R, Chouraki V, Helmer C, Lambert J-C, Metzger M, Stengel B, Lehtimaki T, Lyytikainen L-P, Raitakari O, Johnson A, Parsa A, Bochud M, Heid IM, Goessling W, Kottgen A, Kao WHL, Fox CS, Boeger CAet al., 2015, Genome-wide association study of kidney function decline in individuals of European descent, KIDNEY INTERNATIONAL, Vol: 87, Pages: 1017-1029, ISSN: 0085-2538

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• Citations: 99

Chaker L, Buitendijk GHS, Dehghan A, Medici M, Hofman A, Vingerling JR, Franco OH, Klaver CCW, Peeters RPet al., 2015, Thyroid function and age-related macular degeneration: a prospective population-based cohort study - <i>the Rotterdam Study</i>, BMC MEDICINE, Vol: 13, ISSN: 1741-7015

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• Citations: 45

Freitag DF, Butterworth AS, Willeit P, Howson JMM, Burgess S, Kaptoge S, Young R, Ho WK, Wood AM, Sweeting M, Spackman S, Staley JR, Ramond A, Harshfield E, Nielsen SF, Grande P, Lange LA, Bown MJ, Jones GT, Scott RA, Bevan S, Porcu E, Thorleifsson G, Zeng L, Kessler T, Nikpay M, Do R, Zhang W, Hopewell JC, Kleber M, Delgado GE, Nelson CP, Goel A, Bis JC, Dehghan A, Ligthart S, Smith AV, Qu L, van 't Hof FNG, de Bakker PIW, Baas AF, van Rij A, Tromp G, Kuivaniemi H, Ritchie MD, Verma SS, Crawford DC, Malinowski J, de Andrade M, Kullo IJ, Peissig PL, McCarty CA, Boettinger EP, Gottesman O, Crosslin DR, Carrell DS, Rasmussen-Torvik LJ, Pacheco JA, Huang J, Timpson NJ, Kettunen J, Ala-Korpela M, Mitchell GF, Parsa A, Wilkinson IB, Gorski M, Li Y, Franceschini N, Keller MF, Ganesh SK, Langefeld CD, Bruijn L, Brown MA, Evans DM, Baltic S, Ferreira MA, Baurecht H, Weidinger S, Franke A, Lubitz SA, Mueller-Nurasyid M, Felix JF, Smith NL, Sudman M, Thompson SD, Zeggini E, Panoutsopoulou K, Nalls MA, Singleton A, Polychronakos C, Bradfield JP, Hakonarson H, Easton DF, Thompson D, Tomlinson IP, Dunlop M, Hemminki K, Morgan G, Eisen T, Goldschmidt H, Allan JM, Henrion M, Whiffin N, Wang Y, Chubb D, Houlston RS, Iles MM, Bishop DT, Law MH, Hayward NK, Luo Y, Nejentsev S, Barbalic M, Crossman D, Sanna S, Soranzo N, Markus HS, Wareham NJ, Rader DJ, Reilly M, Assimes T, Harris TB, Hofman A, Franco OH, Gudnason V, Tracy R, Psaty BM, Farrall M, Watkins H, Hall AS, Samani NJ, Maerz W, Clarke R, Collins R, Kooner JS, Chambers JC, Kathiresan S, McPherson R, Erdmann J, Kastrati A, Schunkert H, Stefansson K, Thorsteinsdottir U, Walston JD, Tybjaerg-Hansen A, Alam DS, Majumder AAS, Di Angelantonio E, Chowdhury R, Nordestgaard BG, Saleheen D, Thompson SG, Danesh Jet al., 2015, Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis, LANCET DIABETES & ENDOCRINOLOGY, Vol: 3, Pages: 243-253, ISSN: 2213-8587

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• Citations: 90

Yu B, Li AH, Muzny D, Veeraraghavan N, de Vries PS, Bis JC, Musani SK, Alexander D, Morrison AC, Franco OH, Uitterlinden A, Hofman A, Dehghan A, Wilson JG, Psaty BM, Gibbs R, Wei P, Boerwinkle Eet al., 2015, Association of Rare Loss-Of-Function Alleles in <i>HAL</i>, Serum Histidine Levels and Incident Coronary Heart Disease, CIRCULATION-CARDIOVASCULAR GENETICS, Vol: 8, Pages: 351-355, ISSN: 1942-325X

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• Citations: 33

Postmus I, Deelen J, Sedaghat S, Trompet S, de Craen AJM, Heijmans BT, Franco OH, Hofman A, Dehghan A, Slagboom PE, Westendorp RGJ, Jukema JWet al., 2015, LDL cholesterol still a problem in old age? A Mendelian randomization study, INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, Vol: 44, Pages: 604-612, ISSN: 0300-5771

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• Citations: 38

Haegg S, Fall T, Ploner A, Maegi R, Fischer K, Draisma HHM, Kals M, de Vries PS, Dehghan A, Willems SM, Sarin A-P, Kristiansson K, Nuotio M-L, Havulinna AS, de Bruijn RFAG, Ikram MA, Kuningas M, Stricker BH, Franco OH, Benyamin B, Gieger C, Hall AS, Huikari V, Jula A, Jarvelin M-R, Kaakinen M, Kaprio J, Kobl M, Mangino M, Nelson CP, Palotie A, Samani NJ, Spector TD, Strachan DP, Tobin MD, Whitfield JB, Uitterlinden AG, Salomaa V, Syvanen A-C, Kuulasmaa K, Magnusson PK, Esko T, Hofman A, de Geus EJC, Lind L, Giedraitis V, Perola M, Evans A, Ferrieres J, Virtamo J, Kee F, Tregouet D-A, Arveiler D, Amouyel P, Gianfagna F, Brambilla P, Ripatti S, van Duijn CM, Metspalu A, Prokopenko I, McCarthy MI, Pedersen NL, Ingelsson Eet al., 2015, Adiposity as a cause of cardiovascular disease: a Mendelian randomization study, INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, Vol: 44, Pages: 578-586, ISSN: 0300-5771

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• Citations: 98

de Vries PS, Kavousi M, Ligthart S, Uitterlinden AG, Hofman A, Franco OH, Dehghan Aet al., 2015, Incremental predictive value of 152 single nucleotide polymorphisms in the 10-year risk prediction of incident coronary heart disease: the Rotterdam Study, INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, Vol: 44, Pages: 682-688, ISSN: 0300-5771

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• Citations: 41

Huffman JE, Albrecht E, Teumer A, Mangino M, Kapur K, Johnson T, Kutalik Z, Pirastu N, Pistis G, Lopez LM, Haller T, Salo P, Goel A, Li M, Tanaka T, Dehghan A, Ruggiero D, Malerba G, Smith AV, Nolte IM, Portas L, Phipps-Green A, Boteva L, Navarro P, Johansson A, Hicks AA, Polasek O, Esko T, Peden JF, Harris SE, Murgia F, Wild SH, Tenesa A, Tin A, Mihailov E, Grotevendt A, Gislason GK, Coresh J, D'Adamo P, Ulivi S, Vollenweider P, Waeber G, Campbell S, Kolcic I, Fisher K, Viigimaa M, Metter JE, Masciullo C, Trabetti E, Bombieri C, Sorice R, Doering A, Reischl E, Strauch K, Hofman A, Uitterlinden AG, Waldenberger M, Wichmann H-E, Davies G, Gow AJ, Dalbeth N, Stamp L, Smit JH, Kirin M, Nagaraja R, Nauck M, Schurmann C, Budde K, Farrington SM, Theodoratou E, Jula A, Salomaa V, Sala C, Hengstenberg C, Burnier M, Maegi R, Klopp N, Kloiber S, Schipf S, Ripatti S, Cabras S, Soranzo N, Homuth G, Nutile T, Munroe PB, Hastie N, Campbell H, Rudan I, Cabrera C, Haley C, Franco OH, Merriman TR, Gudnason V, Pirastu M, Penninx BW, Snieder H, Metspalu A, Ciullo M, Pramstaller PP, van Duijn CM, Ferrucci L, Gambaro G, Deary IJ, Dunlop MG, Wilson JF, Gasparini P, Gyllensten U, Spector TD, Wright AF, Hayward C, Watkins H, Perola M, Bochud M, Kao WHL, Caulfield M, Toniolo D, Voelzke H, Gieger C, Koettgen A, Vitart Vet al., 2015, Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans, PLOS ONE, Vol: 10, ISSN: 1932-6203

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• Citations: 32

Huan T, Esko T, Peters MJ, Pilling LC, Schramm K, Schurmann C, Chen BH, Liu C, Joehanes R, Johnson AD, Yao C, Ying S-X, Courchesne P, Milani L, Raghavachari N, Wang R, Liu P, Reinmaa E, Dehghan A, Hofman A, Uitterlinden AG, Hernandez DG, Bandinelli S, Singleton A, Melzer D, Metspalu A, Carstensen M, Grallert H, Herder C, Meitinger T, Peters A, Roden M, Waldenberger M, Doerr M, Felix SB, Zeller T, Vasan R, O'Donnell CJ, Munson PJ, Yang X, Prokisch H, Voelker U, van Meurs JBJ, Ferrucci L, Levy Det al., 2015, A meta-analysis of gene expression signatures of blood pressure and hypertension, PLoS Genetics, Vol: 11, ISSN: 1553-7390

Genome-wide association studies (GWAS) have uncovered numerous genetic variants (SNPs) that are associated with blood pressure (BP). Genetic variants may lead to BP changes by acting on intermediate molecular phenotypes such as coded protein sequence or gene expression, which in turn affect BP variability. Therefore, characterizing genes whose expression is associated with BP may reveal cellular processes involved in BP regulation and uncover how transcripts mediate genetic and environmental effects on BP variability. A meta-analysis of results from six studies of global gene expression profiles of BP and hypertension in whole blood was performed in 7017 individuals who were not receiving antihypertensive drug treatment. We identified 34 genes that were differentially expressed in relation to BP (Bonferroni-corrected p<0.05). Among these genes, FOS and PTGS2 have been previously reported to be involved in BP-related processes; the others are novel. The top BP signature genes in aggregate explain 5%–9% of inter-individual variance in BP. Of note, rs3184504 in SH2B3, which was also reported in GWAS to be associated with BP, was found to be a trans regulator of the expression of 6 of the transcripts we found to be associated with BP (FOS, MYADM, PP1R15A, TAGAP, S100A10, and FGBP2). Gene set enrichment analysis suggested that the BP-related global gene expression changes include genes involved in inflammatory response and apoptosis pathways. Our study provides new insights into molecular mechanisms underlying BP regulation, and suggests novel transcriptomic markers for the treatment and prevention of hypertension.

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Ligthart S, de Vries PS, Uitterlinden AG, Hofman A, Franco OH, Chasman DI, Dehghan Aet al., 2015, Pleiotropy among common genetic loci identified for cardiometabolic disorders and C-reactive protein, PLoS One, Vol: 10, Pages: 1-17, ISSN: 1932-6203

Pleiotropic genetic variants have independent effects on different phenotypes. C-reactive protein (CRP) is associated with several cardiometabolic phenotypes. Shared genetic backgrounds may partially underlie these associations. We conducted a genome-wide analysis to identify the shared genetic background of inflammation and cardiometabolic phenotypes using published genome-wide association studies (GWAS). We also evaluated whether the pleiotropic effects of such loci were biological or mediated in nature. First, we examined whether 283 common variants identified for 10 cardiometabolic phenotypes in GWAS are associated with CRP level. Second, we tested whether 18 variants identified for serum CRP are associated with 10 cardiometabolic phenotypes. We used a Bonferroni corrected p-value of 1.1×10-04 (0.05/463) as a threshold of significance. We evaluated the independent pleiotropic effect on both phenotypes using individual level data from the Women Genome Health Study. Evaluating the genetic overlap between inflammation and cardiometabolic phenotypes, we found 13 pleiotropic regions. Additional analyses showed that 6 regions (APOC1, HNF1A, IL6R, PPP1R3B, HNF4A and IL1F10) appeared to have a pleiotropic effect on CRP independent of the effects on the cardiometabolic phenotypes. These included loci where individuals carrying the risk allele for CRP encounter higher lipid levels and risk of type 2 diabetes. In addition, 5 regions (GCKR, PABPC4, BCL7B, FTO and TMEM18) had an effect on CRP largely mediated through the cardiometabolic phenotypes. In conclusion, our results show genetic pleiotropy among inflammation and cardiometabolic phenotypes. In addition to reverse causation, our data suggests that pleiotropic genetic variants partially underlie the association between CRP and cardiometabolic phenotypes.

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Versmissen J, Oosterveer DM, Yazdanpanah M, Dehghan A, Holm H, Erdman J, Aulchenko YS, Thorleifsson G, Schunkert H, Huijgen R, Vongpromek R, Uitterlinden AG, Defesche JC, van Duijn CM, Mulder M, Dadd T, Karlsson HD, Ordovas J, Kindt I, Jarman A, Hofman A, van Vark-van der Zee L, Blommesteijn-Touw AC, Kwekkeboom J, Liem AH, van der Ouderaa FJ, Calandra S, Bertolini S, Averna M, Langslet G, Ose L, Ros E, Almagro F, de Leeuw PW, Civeira F, Masana L, Pinto X, Simoons ML, Schinkel AFL, Green MR, Zwinderman AH, Johnson KJ, Schaefer A, Neil A, Witteman JCM, Humphries SE, Kastelein JJP, Sijbrands EJGet al., 2015, Identifying genetic risk variants for coronary heart disease in familial hypercholesterolemia: an extreme genetics approach, EUROPEAN JOURNAL OF HUMAN GENETICS, Vol: 23, Pages: 381-387, ISSN: 1018-4813

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• Citations: 12

Shungin D, Winkler TW, Croteau-Chonka DC, Ferreira T, Lockes AE, Maegi R, Strawbridge RJ, Pers TH, Fischer K, Justice AE, Workalemahu T, Wu JMW, Buchkovich ML, Heard-Costa NL, Roman TS, Drong AW, Song C, Gustafsson S, Day FR, Esko T, Fall T, Kutalik Z, Luan J, Randall JC, Scherag A, Vedantam S, Wood AR, Chen J, Fehrmann R, Karjalainen J, Kahali B, Liu C-T, Schmidt EM, Absher D, Amin N, Anderson D, Beekman M, Bragg-Gresham JL, Buyske S, Demirkan A, Ehret GB, Feitosa MF, Goel A, Jackson AU, Johnson T, Kleber ME, Kristiansson K, Mangino M, Leach IM, Medina-Gomez C, Palmer CD, Pasko D, Pechlivaniss S, Peters MJ, Prokopenko I, Stancakova A, Sung YJ, Tanakam T, Teumer A, Van Vliet-Ostaptchouk JV, Yengo L, Zhang W, Albrecht E, Arnlov J, Arscott GM, Bandinelli S, Barrett A, Bellis C, Bennett AJ, Berne C, Blueher M, Buhringer S, Bonnet F, Boettcher Y, Bruinenberg M, Carba DB, Caspersen IH, Clarke R, Daw EW, Deelen J, Deelman E, Delgado G, Doney ASF, Eklund N, Erdos MR, Estrada K, Eury E, Friedrichs N, Garcia ME, Giedraitis V, Gigante B, Go AS, Golay A, Grallert H, Grammer TB, Graessler J, Grewal J, Groves CJ, Haller T, Hallmans G, Hartman CA, Hassinen M, Hayward C, Heikkila K, Herzig K-H, Helmer Q, Hillege HL, Holmen O, Hunt SC, Isaacs A, Ittermann T, James AL, Johansson I, Juliusdottir T, Kalafati I-P, Kinnunen L, Koenig W, Kooner IK, Kratzer W, Lamina C, Leander K, Lee NR, Lichtner P, Lind L, Lindstrom J, Lobbens S, Lorentzon M, Mach F, Magnusson PKE, Mahajan A, McArdle WL, Menni C, Merger S, Mihailov E, Milani L, Mills R, Moayyeri A, Monda KL, Mooijaart SP, Muehleisen TW, Mulas A, Mueller G, Mueller-Nurasyid M, Nagaraja R, Nalls MA, Narisu N, Glorioso N, Nolte IM, Olden M, Rayner NW, Renstrom F, Ried JS, Robertson NR, Rose LM, Sanna S, Scharnagl H, Scholtens S, Sennblad B, Seufferlein T, Sitlani CM, Smith AV, Stirrups K, Stringham HM, Sundstrom J, Swertz MA, Swift AJ, Syvanen A-C, Tayo BO, Thorand B, Thorleifsson G, Tomaschitz A, Troffa C, van Oort FVA, Verweij N, Vonk JMet al., 2015, New genetic loci link adipose and insulin biology to body fat distribution, NATURE, Vol: 518, Pages: 187-U378, ISSN: 0028-0836

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• Citations: 989

Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, Day FR, Powell C, Vedantam S, Buchkovich ML, Yang J, Croteau-Chonka DC, Esko T, Fall T, Ferreira T, Gustafsson S, Kutalik Z, Luan J, Maegi R, Randall JC, Winkler TW, Wood AR, Workalemahu T, Faul JD, Smith JA, Zhao JH, Zhao W, Chen J, Fehrmann R, Hedman AK, Karjalainen J, Schmidt EM, Absher D, Amin N, Anderson D, Beekman M, Bolton JL, Bragg-Gresham L, Buyske S, Demirkan A, Deng G, Ehret GB, Feenstra B, Feitosa MF, Fischer K, Goel A, Gong J, Jackson AU, Kanoni S, Kleber ME, Kristiansson K, Lim U, Lotay V, Mangino M, Leach IM, Medina-Gomez C, Medland SE, Nalls MA, Palmer CD, Pasko D, Pechlivanis S, Peters MJ, Prokopenko I, Shungin D, Stancakova A, Strawbridge RJ, Sung YJ, Tanaka T, Teumer A, Trompet S, van der Laan SW, van Settee J, Van Vliet-Ostaptchouk JV, Wang Z, Yengo L, Zhang W, Isaacs A, Albrecht E, Arnlov J, Arscott GM, Attwood AP, Bandinelli S, Barrett A, Bas IN, Bellis C, Bennett AJ, Berne C, Blagieva R, Blueher M, Bohringer S, Bonnycastle LL, Boettcher Y, Boyd HA, Bruinenberg M, Caspersen IH, Chen Y-DI, Clarke R, Daw EW, de Craen AJM, Delgado G, Dimitriou M, Doney ASF, Eklund N, Estrada K, Eury E, Folkersen L, Fraser RM, Garcia ME, Geller F, Giedraitis V, Gigante B, Go AS, Golay A, Goodall AH, Gordon SD, Gorski M, Grabe H-J, Grallert H, Grammer TB, Graessler J, Gronberg H, Groves CJ, Gusto G, Haessler J, Hall P, Haller T, Hallmans G, Hartman CA, Hassinen M, Hayward C, Heard-Costa NL, Helmer Q, Hengstenberg C, Holmen O, Hottenga J-J, James AL, Jeff JM, Johansson A, Jolley J, Juliusdottir T, Kinnunen L, Koenig W, Koskenvuo M, Kratzer W, Laitinen J, Lamina C, Leander K, Lee NR, Lichtner P, Lind L, Lindstrom J, Lo KS, Lobbens S, Lorbeer R, Lu Y, Mach F, Magnusson PKE, Mahajan A, McArdle WL, McLachlan S, Menni C, Merger S, Mihailov E, Milani L, Moayyeri A, Monda KL, Morken MA, Mulas A, Mueller G, Mueller-Nurasyid M, Musk AW, Nagaraja R, Noethen MM, Nolte IM, Pilz S, Rayner NW, Renstrom F, Rettig R, Ried JS, Ripkeet al., 2015, Genetic studies of body mass index yield new insights for obesity biology, Nature, Vol: 518, Pages: 197-206, ISSN: 0028-0836

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Ghanbari M, Sedaghat S, de Looper HWJ, Hofman A, Erkeland SJ, Franco OH, Dehghan Aet al., 2015, The Association of Common Polymorphisms in miR-196a2 with Waist to Hip Ratio and miR-1908 with Serum Lipid and Glucose, OBESITY, Vol: 23, Pages: 495-503, ISSN: 1930-7381

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• Citations: 24

Wessel J, Chu AY, Willems SM, Wang S, Yaghootkar H, Brody JA, Dauriz M, Hivert M-F, Raghavan S, Lipovich L, Hidalgo B, Fox K, Huffman JE, An P, Lu Y, Rasmussen-Torvik LJ, Grarup N, Ehm MG, Li L, Baldridge AS, Stancakova A, Abrol R, Besse C, Boland A, Bork-Jensen J, Fornage M, Freitag DF, Garcia ME, Guo X, Hara K, Isaacs A, Jakobsdottir J, Lange LA, Layton JC, Li M, Zhao JH, Meidtner K, Morrison AC, Nalls MA, Peters MJ, Sabater-Lleal M, Schurmann C, Silveira A, Smith AV, Southam L, Stoiber MH, Strawbridge RJ, Taylor KD, Varga TV, Allin KH, Amin N, Aponte JL, Aung T, Barbieri C, Bihlmeyer NA, Boehnke M, Bombieri C, Bowden DW, Burns SM, Chen Y, Chen Y-D, Cheng C-Y, Correa A, Czajkowski J, Dehghan A, Ehret GB, Eiriksdottir G, Escher SA, Farmaki A-E, Franberg M, Gambaro G, Giulianini F, Goddard WA, Goel A, Gottesman O, Grove ML, Gustafsson S, Hai Y, Hallmans G, Heo J, Hoffmann P, Ikram MK, Jensen RA, Jorgensen ME, Jorgensen T, Karaleftheri M, Khor CC, Kirkpatrick A, Kraja AT, Kuusisto J, Lange EM, Lee IT, Lee W-J, Leong A, Liao J, Liu C, Liu Y, Lindgren CM, Linneberg A, Malerba G, Mamakou V, Marouli E, Maruthur NM, Matchan A, McKean-Cowdin R, McLeod O, Metcalf GA, Mohlke KL, Muzny DM, Ntalla I, Palmer ND, Pasko D, Peter A, Rayner NW, Renstroem F, Rice K, Sala CF, Sennblad B, Serafetinidis I, Smith JA, Soranzo N, Speliotes EK, Stahl EA, Stirrups K, Tentolouris N, Thanopoulou A, Torres M, Traglia M, Tsafantakis E, Javad S, Yanek LR, Zengini E, Becker DM, Bis JC, Brown JB, Cupples LA, Hansen T, Ingelsson E, Karter AJ, Lorenzo C, Mathias RA, Norris JM, Peloso GM, Sheu WH-H, Toniolo D, Vaidya D, Varma R, Wagenknecht LE, Boeing H, Bottinger EP, Dedoussis G, Deloukas P, Ferrannini E, Franco OH, Franks PW, Gibbs RA, Gudnason V, Hamsten A, Harris TB, Hattersley AT, Hayward C, Hofman A, Jansson J-H, Langenberg C, Launer LJ, Levy D, Oostra BA, O'Donnell CJ, O'Rahilly S, Padmanabhan S, Pankow JS, Polasek O, Province MA, Rich SS, Ridker PM, Rudan I, Schulze MB, Smith BH, Uitterlindenet al., 2015, Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility, Nature Communications, Vol: 6, ISSN: 2041-1723

Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore therole of coding variation on these traits by analysis of variants on the HumanExome BeadChipin 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify anovel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492;MAF ¼ 1.4%) with lower FG (b ¼ 0.09±0.01 mmol l 1, P ¼ 3.4 10 12), T2D risk(OR[95%CI] ¼ 0.86[0.76–0.96], P ¼ 0.010), early insulin secretion (b ¼ 0.07±0.035pmolinsulin mmolglucose 1 , P ¼ 0.048), but higher 2-h glucose (b ¼ 0.16±0.05 mmol l 1,P ¼ 4.3 10 4). We identify a gene-based association with FG at G6PC2(pSKAT ¼ 6.8 10 6) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X andS324P). We identify rs651007 (MAF ¼ 20%) in the first intron of ABO at the putativepromoter of an antisense lncRNA, associating with higher FG (b ¼ 0.02±0.004 mmol l 1,P ¼ 1.3 10 8). Our approach identifies novel coding variant associations and extendsthe allelic spectrum of variation underlying diabetes-related quantitative traits and T2Dsusceptibility.DOI: 10.103

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Baumert J, Huang J, McKnight B, Sabater-Lleal M, Steri M, Chu AY, Trompet S, Lopez LM, Fornage M, Teumer A, Tang W, Rudnicka AR, Maelarstig A, Hottenga J-J, Kavousi M, Lahti J, Tanaka T, Hayward C, Huffman JE, Morange P-E, Rose LM, Basu S, Rumley A, Stott DJ, Buckley BM, de Craen AJM, Sanna S, Masala M, Biffar R, Homuth G, Silveira A, Sennblad B, Goel A, Watkins H, Mueller-Nurasyid M, Rueckerl R, Taylor K, Chen M-H, de Geus EJC, Hofman A, Witteman JCM, de Maat MPM, Palotie A, Davies G, Siscovick DS, Kolcic I, Wild SH, Song J, McArdle WL, Ford I, Sattar N, Schlessinger D, Grotevendt A, Franzosi MG, Illig T, Waldenberger M, Lumley T, Tofler GH, Willemsen G, Uitterlinden AG, Rivadeneira F, Raeikkonen K, Chasman DI, Folsom AR, Lowe GD, Westendorp RGJ, Slagboom PE, Cucca F, Wallaschofski H, Strawbridge RJ, Seedorf U, Koenig W, Bis JC, Mukamal KJ, van Dongen J, Widen E, Franco OH, Starr JM, Liu K, Ferrucci L, Polasek O, Wilson JF, Oudot-Mellakh T, Campbell H, Navarro P, Bandinelli S, Eriksson J, Boomsma DI, Dehghan A, Clarke R, Hamsten A, Boerwinkle E, Jukema JW, Naitza S, Ridker PM, Voezke H, Deary IJ, Reiner AP, Tregoueet D-A, O'Donnell CJ, Strachan DP, Peters A, Smith NLet al., 2014, No Evidence for Genome-Wide Interactions on Plasma Fibrinogen by Smoking, Alcohol Consumption and Body Mass Index: Results from Meta-Analyses of 80,607 Subjects, PLOS ONE, Vol: 9, ISSN: 1932-6203

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• Citations: 5

Franceschini N, Hu Y, Reiner AP, Buyske S, Nalls M, Yanek LR, Li Y, Hindorff LA, Cole SA, Howard BV, Stafford JM, Carty CL, Sethupathy P, Martin LW, Lin D-Y, Johnson KC, Becker LC, North KE, Dehghan A, Bis JC, Liu Y, Greenland P, Manson JE, Maeda N, Garcia M, Harris TB, Becker DM, O'Donnell C, Heiss G, Kooperberg C, Boerwinkle Eet al., 2014, Prospective Associations of Coronary Heart Disease Loci in African Americans Using the MetaboChip: The PAGE Study, PLOS ONE, Vol: 9, ISSN: 1932-6203

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• Citations: 17

Keller MF, Reiner AP, Okada Y, van Rooij FJA, Johnson AD, Chen M-H, Smith AV, Morris AP, Tanaka T, Ferrucci L, Zonderman AB, Lettre G, Harris T, Garcia M, Bandinelli S, Qayyum R, Yanek LR, Becker DM, Becker LC, Kooperberg C, Keating B, Reis J, Tang H, Boerwinkle E, Kamatani Y, Matsuda K, Kamatani N, Nakamura Y, Kubo M, Liu S, Dehghan A, Felix JF, Hofman A, Uitterlinden AG, van Duijn CM, Franco OH, Longo DL, Singleton AB, Psaty BM, Evans MK, Cupples LA, Rotter JI, O'Donnell CJ, Takahashi A, Wilson JG, Ganesh SK, Nalls MAet al., 2014, Trans-ethnic meta-analysis of white blood cell phenotypes, HUMAN MOLECULAR GENETICS, Vol: 23, Pages: 6944-6960, ISSN: 0964-6906

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• Citations: 49

Rodenburg EM, Hofland J, Van Noord C, Visser LE, Dehghan A, Barbalic M, Jan Danser AH, Lawson KS, Hofman A, Witteman J, Boerwinkle E, Uitterlinden AG, Stricker BH, De Jong FHet al., 2014, Sex-specific differences in the effects of local androgen metabolism in the heart as an indicator for the risk of myocardial infarction, Cardiovascular Endocrinology, Vol: 3, Pages: 134-141

Aim Testosterone influences cardiovascular risk and disease in a sex-specific manner. The more potent androgen 5α-dihydrotestosterone (DHT) can be formed through conversion of testosterone by the enzyme 5α-reductase. We hypothesized that, because of the presence of DHT in coronary and myocardial tissues, a sexually dimorphic effect can be observed if differences exist in genetics or mRNA expression in androgen-metabolizing enzymes. Materials and methods mRNA levels of steroidogenic enzymes and the androgen receptor (AR) were investigated in human myocardial tissue samples. Subsequently, all participants in the baseline cohort of the Rotterdam Study (RSI) with successful genotyping and without prevalent myocardial infarction (MI, N=5199) were recruited to study the association between single nucleotide polymorphisms (SNPs) within SRD5A1, SRD5A2, and AKR1C3 and incident MI using Cox regression models. Significant results were replicated within the Atherosclerosis Risk in Communities cohort and the second cohort of the RSII. Results The expression of SRD5A1, AKR1C3, and AR was found in all myocardial samples, whereas HSD17B3 and SRD5A2 expression levels were low and undetectable, respectively. Myocardial SRD5A1 expression was higher in women than in men. Within SRD5A1, SNP rs248805G>A was significantly associated with incident MI in western European women (hazard ratio 1.49; 95% confidence interval 1.19-1.87). This SNP is tightly linked to the HinfI polymorphism in SRD5A1 (rs248793G>C), of which the minor allele has been associated with a higher DHT/T ratio. Conclusion Genetic variation in SRD5A1 is associated with an increased risk of MI in western European women, possibly because of the sex-specific potential of local androgen conversion and effect.

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Ligthart S, Sedaghat S, Ikram MA, Hofman A, Franco OH, Dehghan Aet al., 2014, EN-RAGE A Novel Inflammatory Marker for Incident Coronary Heart Disease, ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, Vol: 34, Pages: 2695-2699, ISSN: 1079-5642

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• Citations: 49

Ghanbari M, de Vries PS, de Looper H, Peters MJ, Schurmann C, Yaghootkar H, Doerr M, Frayling TM, Uitterlinden AG, Hofman A, van Meurs JBJ, Erkeland SJ, Franco OH, Dehghan Aet al., 2014, A Genetic Variant in the Seed Region of miR-4513 Shows Pleiotropic Effects on Lipid and Glucose Homeostasis, Blood Pressure, and Coronary Artery Disease, HUMAN MUTATION, Vol: 35, Pages: 1524-1531, ISSN: 1059-7794

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• Citations: 37

Sedaghat S, Pazoki R, Uitterlinden AG, Hofman A, Stricker BHC, Ikram MA, Franco OH, Dehghan Aet al., 2014, Association of Uric Acid Genetic Risk Score With Blood Pressure The Rotterdam Study, HYPERTENSION, Vol: 64, Pages: 1061-+, ISSN: 0194-911X

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• Citations: 29

Chaker L, Baumgartner C, Ikram MA, Dehghan A, Medici M, Visser WE, Hofman A, Rodondi N, Peeters RP, Franco OHet al., 2014, Subclinical thyroid dysfunction and the risk of stroke: a systematic review and meta-analysis, EUROPEAN JOURNAL OF EPIDEMIOLOGY, Vol: 29, Pages: 791-800, ISSN: 0393-2990

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• Citations: 38

Sedaghat S, Arce FGD, Verwoert GC, Hofman A, Ikram MA, Franco OH, Dehghan A, Witteman JCM, Mattace-Raso Fet al., 2014, Association of renal function with vascular stiffness in older adults: the Rotterdam study, AGE AND AGEING, Vol: 43, Pages: 827-833, ISSN: 0002-0729

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• Citations: 13