DrPaulO'Reilly

Cheng G, Tang CS-M, Wong EH-M, Cheng WW-C, So M-T, Miao X, Zhang R, Cui L, Liu X, Ngan ES-W, Lui VC-H, Chung PH-Y, Chan IH-Y, Liu J, Zhong W, Xia H, Yu J, Qiu X, Wu X-Z, Wang B, Dong X, Tou J, Huang L, Yi B, Ren H, Chan EK-W, Ye K, O'Reilly PF, Wong KK-Y, Sham P-C, Cherny SS, Tam PK-H, Garcia-Barcelo M-Met al., 2013, Common genetic variants regulating ADD3 gene expression alter biliary atresia risk, JOURNAL OF HEPATOLOGY, Vol: 59, Pages: 1285-1291, ISSN: 0168-8278

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• Citations: 45

Song Y-Q, Karasugi T, Cheung KMC, Chiba K, Ho DWH, Miyake A, Kao PYP, Sze KL, Yee A, Takahashi A, Kawaguchi Y, Mikami Y, Matsumoto M, Togawa D, Kanayama M, Shi D, Dai J, Jiang Q, Wu C, Tian W, Wang N, Leong JCY, Luk KDK, Yip S-P, Cherny SS, Wang J, Mundlos S, Kelempisioti A, Eskola PJ, Maennikkoe M, Maekelae P, Karppinen J, Jarvelin M-R, O'Reilly PF, Kubo M, Kimura T, Kubo T, Toyama Y, Mizuta H, Cheah KSE, Tsunoda T, Sham P-C, Ikegawa S, Chan Det al., 2013, Lumbar disc degeneration is linked to a carbohydrate sulfotransferase 3 variant, JOURNAL OF CLINICAL INVESTIGATION, Vol: 123, Pages: 4909-4917, ISSN: 0021-9738

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• Citations: 65

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: 189

Kujala UM, Makinen V-P, Heinonen I, Soininen P, Kangas AJ, Leskinen TH, Rahkila P, Wurtz P, Kovanen V, Cheng S, Sipila S, Telama R, Tammelin T, Savolainen MJ, Pouta A, O'Reilly PF, Mantyselka P, Viikari J, Kahonen M, Lehtimaki T, Elliott P, Vanhala MJ, Raitakari OT, Jarvelin M-R, Kaprio J, Kainulainen H, Ala-Korpela Met al., 2013, Long-term Leisure-time Physical Activity and Serum Metabolome, CIRCULATION, Vol: 127, Pages: 340-+, ISSN: 0009-7322

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• Citations: 121

al Basatena N-KS, Hoggart CJ, Coin LJ, O'Reilly PFet al., 2013, The Effect of Genomic Inversions on Estimation of Population Genetic Parameters from SNP Data, GENETICS, Vol: 193, Pages: 243-253, ISSN: 0016-6731

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• Citations: 9

Codd V, Nelson CP, Albrecht E, Mangino M, Deelen J, Buxton JL, Hottenga JJ, Fischer K, Esko T, Surakka I, Broer L, Nyholt DR, Mateo Leach I, Salo P, Hagg S, Matthews MK, Palmen J, Norata GD, O'Reilly PF, Saleheen D, Amin N, Balmforth AJ, Beekman M, de Boer RA, Bohringer S, Braund PS, Burton PR, de Craen AJ, Denniff M, Dong Y, Douroudis K, Dubinina E, Eriksson JG, Garlaschelli K, Guo D, Hartikainen AL, Henders AK, Houwing-Duistermaat JJ, Kananen L, Karssen LC, Kettunen J, Klopp N, Lagou V, van Leeuwen EM, Madden PA, Magi R, Magnusson PK, Mannisto S, McCarthy MI, Medland SE, Mihailov E, Montgomery GW, Oostra BA, Palotie A, Peters A, Pollard H, Pouta A, Prokopenko I, Ripatti S, Salomaa V, Suchiman HE, Valdes AM, Verweij N, Vinuela A, Wang X, Wichmann HE, Widen E, Willemsen G, Wright MJ, Xia K, Xiao X, van Veldhuisen DJ, Catapano AL, Tobin MD, Hall AS, Blakemore AI, van Gilst WH, Zhu H, Consortium C, Erdmann J, Reilly MP, Kathiresan S, Schunkert H, Talmud PJ, Pedersen NL, Perola M, Ouwehand W, Kaprio J, Martin NG, van Duijn CM, Hovatta I, Gieger C, Metspalu A, Boomsma DI, Jarvelin MR, Slagboom PE, Thompson JR, Spector TD, van der Harst P, Samani NJet al., 2013, Identification of seven loci affecting mean telomere length and their association with disease, Nat Genet, Vol: 45, Pages: 422-427e2, ISSN: 1546-1718

Interindividual variation in mean leukocyte telomere length (LTL) is associated with cancer and several age-associated diseases. We report here a genome-wide meta-analysis of 37,684 individuals with replication of selected variants in an additional 10,739 individuals. We identified seven loci, including five new loci, associated with mean LTL (P < 5 x 10(-8)). Five of the loci contain candidate genes (TERC, TERT, NAF1, OBFC1 and RTEL1) that are known to be involved in telomere biology. Lead SNPs at two loci (TERC and TERT) associate with several cancers and other diseases, including idiopathic pulmonary fibrosis. Moreover, a genetic risk score analysis combining lead variants at all 7 loci in 22,233 coronary artery disease cases and 64,762 controls showed an association of the alleles associated with shorter LTL with increased risk of coronary artery disease (21% (95% confidence interval, 5-35%) per standard deviation in LTL, P = 0.014). Our findings support a causal role of telomere-length variation in some age-related diseases.

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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: 215

O'Reilly PF, Hoggart CJ, Pomyen Y, Calboli FCF, Elliott P, Jarvelin M-R, Coin LJMet al., 2012, MultiPhen: Joint Model of Multiple Phenotypes Can Increase Discovery in GWAS, PLOS One, Vol: 7, ISSN: 1932-6203

The genome-wide association study (GWAS) approach has discovered hundreds of genetic variants associated with diseasesand quantitative traits. However, despite clinical overlap and statistical correlation between many phenotypes, GWAS aregenerally performed one-phenotype-at-a-time. Here we compare the performance of modelling multiple phenotypes jointlywith that of the standard univariate approach. We introduce a new method and software, MultiPhen, that models multiplephenotypes simultaneously in a fast and interpretable way. By performing ordinal regression, MultiPhen tests the linearcombination of phenotypes most associated with the genotypes at each SNP, and thus potentially captures effects hiddento single phenotype GWAS. We demonstrate via simulation that this approach provides a dramatic increase in power inmany scenarios. There is a boost in power for variants that affect multiple phenotypes and for those that affect only onephenotype. While other multivariate methods have similar power gains, we describe several benefits of MultiPhen overthese. In particular, we demonstrate that other multivariate methods that assume the genotypes are normally distributed,such as canonical correlation analysis (CCA) and MANOVA, can have highly inflated type-1 error rates when testing casecontrolor non-normal continuous phenotypes, while MultiPhen produces no such inflation. To test the performance ofMultiPhen on real data we applied it to lipid traits in the Northern Finland Birth Cohort 1966 (NFBC1966). In these dataMultiPhen discovers 21% more independent SNPs with known associations than the standard univariate GWAS approach,while applying MultiPhen in addition to the standard approach provides 37% increased discovery. The most associatedlinear combinations of the lipids estimated by MultiPhen at the leading SNPs accurately reflect the Friedewald Formula,suggesting that MultiPhen could be used to refine the definition of existing phenotypes or uncover novel heritablepheno

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Taal HR, St Pourcain B, Thiering E, Das S, Mook-Kanamori DO, Warrington NM, Kaakinen M, Kreiner-Moller E, Bradfield JP, Freathy RM, Geller F, Guxens M, Cousminer DL, Kerkhof M, Timpson NJ, Ikram MA, Beilin LJ, Bonnelykke K, Buxton JL, Charoen P, Chawes BLK, Eriksson J, Evans DM, Hofman A, Kemp JP, Kim CE, Klopp N, Lahti J, Lye SJ, McMahon G, Mentch FD, Muller-Nurasyid M, O'Reilly PF, Prokopenko I, Rivadeneira F, Steegers EAP, Sunyer J, Tiesler C, Yaghootkar H, Breteler MMB, Debette S, Fornage M, Gudnason V, Launer LJ, van der Lugt A, Mosley TH, Seshadri S, Smith AV, Vernooij MW, Blakemore AIF, Chiavacci RM, Feenstra B, Fernandez-Banet J, Grant SFA, Hartikainen A, van der Heijden AJ, Iniguez C, Lathrop M, McArdle WL, Molgaard A, Newnham JP, Palmer LJ, Palotie A, Pouta A, Ring SM, Sovio U, Standl M, Uitterlinden AG, Wichmann H, Vissing NH, DeCarli C, van Duijn CM, McCarthy MI, Koppelman GH, Estivill X, Hattersley AT, Melbye M, Bisgaard H, Pennell CE, Widen E, Hakonarson H, Smith GD, Heinrich J, Jarvelin M, Jaddoe VWVet al., 2012, Common variants at 12q15 and 12q24 are associated with infant head circumference, Nat Genet, Vol: 44, Pages: 532-538, ISSN: 1061-4036

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Tukiainen T, Kettunen J, Kangas AJ, Lyytikainen L-P, Soininen P, Sarin A-P, Tikkanen E, O'Reilly PF, Savolainen MJ, Kaski K, Pouta A, Jula A, Lehtimaki T, Kahonen M, Viikari J, Taskinen M-R, Jauhiainen M, Eriksson JG, Raitakari O, Salomaa V, Jarvelin M-R, Perola M, Palotie A, Ala-Korpela M, Ripatti Set al., 2012, Detailed metabolic and genetic characterization reveals new associations for 30 known lipid loci, HUMAN MOLECULAR GENETICS, Vol: 21, Pages: 1444-1455, ISSN: 0964-6906

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• Citations: 66

Hoggart CJ, O'Reilly PF, Kaakinen M, Zhang W, Chambers JC, Kooner JS, Coin LJM, Jarvelin M-Ret al., 2012, Fine-Scale Estimation of Location of Birth from Genome-Wide Single-Nucleotide Polymorphism Data, GENETICS, Vol: 190, Pages: 669-U583, ISSN: 0016-6731

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• Citations: 6

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: 279

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: 353

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: 1374

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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O'Reilly PF, Balding DJ, 2011, Admixture provides new insights into recombination, Nature Genetics, Pages: 819-820

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Fox ER, Young JH, Li Y, Dreisbach AW, Keating BJ, Musani SK, Liu K, Morrison AC, Ganesh S, Kutlar A, Ramachandran VS, Polak JF, Fabsitz RR, Dries DL, Farlow DN, Redline S, Adeyemo A, Hirschorn JN, Sun YV, Wyatt SB, Penman AD, Palmas W, Rotter JI, Townsend RR, Doumatey AP, Tayo BO, Mosley TH, Lyon HN, Kang SJ, Rotimi CN, Cooper RS, Franceschini N, Curb JD, Martin LW, Eaton CB, Kardia SL, Taylor HA, Caulfield MJ, Ehret GB, Johnson T, International Consortium for Blood Pressure Genome-wide Association Studies ICBP-GWAS, Chakravarti A, Zhu X, Levy Det al., 2011, Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study., Human Molecular Genetics, Vol: 20, Pages: 2273-2284, ISSN: 1460-2083

The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10(-8)) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10(-8)). The top IBC association for SBP was rs2012318 (P= 6.4 × 10(-6)) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10(-6)) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity.

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Schumann G, Coin LJ, Lourdusamy A, Charoen P, Berger KH, Stacey D, Desrivieres S, Aliev FA, Khan AA, Amin N, Aulchenko YS, Bakalkin G, Bakker SJ, Balkau B, Beulens JW, Bilbao A, de Boer RA, Beury D, Bots ML, Breetvelt EJ, Cauchi S, Cavalcanti-Proenca C, Chambers JC, Clarke T-K, Dahmen N, de Geus EJ, Dick D, Ducci F, Easton A, Edenberg HJ, Esko T, Fernandez-Medarde A, Foroud T, Freimer NB, Girault J-A, Grobbee DE, Guarrera S, Gudbjartsson DF, Hartikainen A-L, Heath AC, Hesselbrock V, Hofman A, Hottenga J-J, Isohanni MK, Kaprio J, Khaw K-T, Kuehnel B, Laitinen J, Lobbens S, Luan J, Mangino M, Maroteaux M, Matullo G, McCarthy MI, Mueller C, Navis G, Numans ME, Nunez A, Nyholt DR, Onland-Moret CN, Oostra BA, O'Reilly PF, Palkovits M, Penninx BW, Polidoro S, Pouta A, Prokopenko I, Ricceri F, Santos E, Smit JH, Soranzo N, Song K, Sovio U, Stumvoll M, Surakk I, Thorgeirsson TE, Thorsteinsdottir U, Troakes C, Tyrfingsson T, Toenjes A, Uiterwaal CS, Uitterlinden AG, van der Harst P, van der Schouw YT, Staehlin O, Vogelzangs N, Vollenweider P, Waeber G, Wareham NJ, Waterworth DM, Whitfield JB, Wichmann EH, Willemsen G, Witteman JC, Yuan X, Zhai G, Zhao JH, Zhang W, Martin NG, Metspalu A, Doering A, Scott J, Spector TD, Loos RJ, Boomsma DI, Mooser V, Peltonen L, Stefansson K, van Duijn CM, Vineis P, Sommer WH, Kooner JS, Spanagel R, Heberlein UA, Jarvelin M-R, Elliott Pet al., 2011, Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption (vol 108, pg 7119, 2011), PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 108, Pages: 9316-9316, ISSN: 0027-8424

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Kraja AT, Vaidya D, Pankow JS, Goodarzi MO, Assimes TL, Kullo IJ, Sovio U, Mathias RA, Sun YV, Franceschini N, Absher D, Li G, Zhang Q, Feitosa MF, Glazer NL, Haritunians T, Hartikainen A-L, Knowles JW, North KE, Iribarren C, Kral B, Yanek L, O'Reilly PF, McCarthy MI, Jaquish C, Couper DJ, Chakravarti A, Psaty BM, Becker LC, Province MA, Boerwinkle E, Quertermous T, Palotie L, Jarvelin M-R, Becker DM, Kardia SLR, Rotter JI, Chen Y-DI, Borecki IBet al., 2011, A bivariate genome-wide approach to metabolic syndrome STAMPEED consortium, Diabetes, Vol: 60, Pages: 1329-1339, ISSN: 0012-1797

OBJECTIVE The metabolic syndrome (MetS) is defined as concomitant disorders of lipid and glucose metabolism, central obesity, and high blood pressure, with an increased risk of type 2 diabetes and cardiovascular disease. This study tests whether common genetic variants with pleiotropic effects account for some of the correlated architecture among five metabolic phenotypes that define MetS.RESEARCH DESIGN AND METHODS Seven studies of the STAMPEED consortium, comprising 22,161 participants of European ancestry, underwent genome-wide association analyses of metabolic traits using a panel of ∼2.5 million imputed single nucleotide polymorphisms (SNPs). Phenotypes were defined by the National Cholesterol Education Program (NCEP) criteria for MetS in pairwise combinations. Individuals exceeding the NCEP thresholds for both traits of a pair were considered affected.RESULTS Twenty-nine common variants were associated with MetS or a pair of traits. Variants in the genes LPL, CETP, APOA5 (and its cluster), GCKR (and its cluster), LIPC, TRIB1, LOC100128354/MTNR1B, ABCB11, and LOC100129150 were further tested for their association with individual qualitative and quantitative traits. None of the 16 top SNPs (one per gene) associated simultaneously with more than two individual traits. Of them 11 variants showed nominal associations with MetS per se. The effects of 16 top SNPs on the quantitative traits were relatively small, together explaining from ∼9% of the variance in triglycerides, 5.8% of high-density lipoprotein cholesterol, 3.6% of fasting glucose, and 1.4% of systolic blood pressure.CONCLUSIONS Qualitative and quantitative pleiotropic tests on pairs of traits indicate that a small portion of the covariation in these traits can be explained by the reported common genetic variants.

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Kilpelaeinen TO, den Hoed M, Ong KK, Grontved A, Brage S, Jameson K, Cooper C, Khaw K-T, Ekelund U, Wareham NJ, Loos RJFet al., 2011, Obesity-susceptibility loci have a limited influence on birth weight: a meta-analysis of up to 28,219 individuals, AMERICAN JOURNAL OF CLINICAL NUTRITION, Vol: 93, Pages: 851-860, ISSN: 0002-9165

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• Citations: 46

Tabara Y, Kohara K, Kita Y, Hirawa N, Katsuya T, Ohkubo T, Hiura Y, Tajima A, Morisaki T, Miyata T, Nakayama T, Takashima N, Nakura J, Kawamoto R, Takahashi N, Hata A, Soma M, Imai Y, Kokubo Y, Okamura T, Tomoike H, Iwai N, Ogihara T, Inoue I, Tokunaga K, Johnson T, Caulfield M, Munroe P, Umemura S, Ueshima H, Miki Tet al., 2010, Common Variants in the ATP2B1 Gene Are Associated With Susceptibility to Hypertension The Japanese Millennium Genome Project, HYPERTENSION, Vol: 56, Pages: 973-U533, ISSN: 0194-911X

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• Citations: 71

Ikram MK, Sim X, Jensen RA, Cotch MF, Hewitt AW, Ikram MA, Wang JJ, Klein R, Klein BE, Breteler MM, Cheung N, Liew G, Mitchell P, Uitterlinden AG, Rivadeneira F, Hofman A, de Jong PT, van Duijn CM, Kao L, Cheng CY, Smith AV, Glazer NL, Lumley T, McKnight B, Psaty BM, Jonasson F, Eiriksdottir G, Aspelund T, Global BPgen Consortium, Harris TB, Launer LJ, Taylor KD, Li X, Iyengar SK, Xi Q, Sivakumaran TA, Mackey DA, Macgregor S, Martin NG, Young TL, Bis JC, Wiggins KL, Heckbert SR, Hammond CJ, Andrew T, Fahy S, Attia J, Holliday EG, Scott RJ, Islam FM, Rotter JI, McAuley AK, Boerwinkle E, Tai ES, Gudnason V, Siscovick DS, Vingerling JR, Wong TYet al., 2010, Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo., PLOS Genetics, Vol: 6, ISSN: 1553-7390

There is increasing evidence that the microcirculation plays an important role in the pathogenesis of cardiovascular diseases. Changes in retinal vascular caliber reflect early microvascular disease and predict incident cardiovascular events. We performed a genome-wide association study to identify genetic variants associated with retinal vascular caliber. We analyzed data from four population-based discovery cohorts with 15,358 unrelated Caucasian individuals, who are members of the Cohort for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and replicated findings in four independent Caucasian cohorts (n  =  6,652). All participants had retinal photography and retinal arteriolar and venular caliber measured from computer software. In the discovery cohorts, 179 single nucleotide polymorphisms (SNP) spread across five loci were significantly associated (p<5.0×10(-8)) with retinal venular caliber, but none showed association with arteriolar caliber. Collectively, these five loci explain 1.0%-3.2% of the variation in retinal venular caliber. Four out of these five loci were confirmed in independent replication samples. In the combined analyses, the top SNPs at each locus were: rs2287921 (19q13; p  =  1.61×10(-25), within the RASIP1 locus), rs225717 (6q24; p = 1.25×10(-16), adjacent to the VTA1 and NMBR loci), rs10774625 (12q24; p  =  2.15×10(-13), in the region of ATXN2,SH2B3 and PTPN11 loci), and rs17421627 (5q14; p = 7.32×10(-16), adjacent to the MEF2C locus). In two independent samples, locus 12q24 was also associated with coronary heart disease and hypertension. Our population-based genome-wide association study demonstrates four novel loci associated with retinal venular caliber, an endophenotype of the microcirculation associated with clinical cardiovascular disease. These data provide further insights into the contribution and biological mechanisms of microcirculatory changes that underlie cardiovascular dis

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Wang TJ, Zhang F, Richards JB, Kestenbaum B, van Meurs JB, Berry D, Kiel DP, Streeten EA, Ohlsson C, Koller DL, Peltonen L, Cooper JD, O'Reilly PF, Houston DK, Glazer NL, Vandenput L, Peacock M, Shi J, Rivadeneira F, McCarthy MI, Anneli P, de Boer IH, Mangino M, Kato B, Smyth DJ, Booth SL, Jacques PF, Burke GL, Goodarzi M, Cheung C-L, Wolf M, Rice K, Goltzman D, Hidiroglou N, Ladouceur M, Wareham NJ, Hocking LJ, Hart D, Arden NK, Cooper C, Malik S, Fraser WD, Hartikainen A-L, Zhai G, Macdonald HM, Forouhi NG, Loos RJF, Reid DM, Hakim A, Dennison E, Liu Y, Power C, Stevens HE, Jaana L, Vasan RS, Soranzo N, Bojunga J, Psaty BM, Lorentzon M, Foroud T, Harris TB, Hofman A, Jonsson J-O, Cauley JA, Uitterlinden AG, Gibson Q, Jarvelin M-R, Karasik D, Siscovick DS, Econs MJ, Kritchevsky SB, Florez JC, Todd JA, Dupuis J, Hyppoenen E, Spector TDet al., 2010, Common genetic determinants of vitamin D insufficiency: a genome-wide association study, LANCET, Vol: 376, Pages: 180-188, ISSN: 0140-6736

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• Citations: 1069

Freathy RM, Mook-Kanamori DO, Sovio U, Prokopenko I, Timpson NJ, Berry DJ, Warrington NM, Widen E, Hottenga JJ, Kaakinen M, Lange LA, Bradfield JP, Kerkhof M, Marsh JA, Maegi R, Chen C-M, Lyon HN, Kirin M, Adair LS, Aulchenko YS, Bennett AJ, Borja JB, Bouatia-Naji N, Charoen P, Coin LJM, Cousminer DL, de Geus EJC, Deloukas P, Elliott P, Evans DM, Froguel P, Glaser B, Groves CJ, Hartikainen A-L, Hassanali N, Hirschhorn JN, Hofman A, Holly JMP, Hyppoenen E, Kanoni S, Knight BA, Laitinen J, Lindgren CM, McArdle WL, O'Reilly PF, Pennell CE, Postma DS, Pouta A, Ramasamy A, Rayner NW, Ring SM, Rivadeneira F, Shields BM, Strachan DP, Surakka I, Taanila A, Tiesler C, Uitterlinden AG, van Duijn CM, Wijga AH, Willemsen G, Zhang H, Zhao J, Wilson JF, Steegers EAP, Hattersley AT, Eriksson JG, Peltonen L, Mohlke KL, Grant SFA, Hakonarson H, Koppelman GH, Dedoussis GV, Heinrich J, Gillman MW, Palmer LJ, Frayling TM, Boomsma DI, Smith GD, Power C, Jaddoe VWV, Jarvelin M-R, McCarthy MIet al., 2010, Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight, NATURE GENETICS, Vol: 42, Pages: 430-U73, ISSN: 1061-4036

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• Citations: 170

O'Reilly PF, Coin LJM, Hoggart CJ, 2010, invertFREGENE: software for simulating inversions in population genetic data, BIOINFORMATICS, Vol: 26, Pages: 838-840, ISSN: 1367-4803

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Pillas D, Hoggart CJ, Evans DM, O'Reilly PF, Sipila K, Lahdesmaki R, Millwood IY, Kaakinen M, Netuveli G, Blane D, Charoen P, Sovio U, Pouta A, Freimer N, Hartikainen A-L, Laitinen J, Vaara S, Glaser B, Crawford P, Timpson NJ, Ring SM, Deng G, Zhang W, McCarthy MI, Deloukas P, Peltonen L, Elliott P, Coin LJM, Smith GD, Jarvelin M-Ret al., 2010, Genome-Wide Association Study Reveals Multiple Loci Associated with Primary Tooth Development during Infancy, PLOS Genetics, Vol: 6, ISSN: 1553-7390

Tooth development is a highly heritable process which relates to other growth and developmental processes, and which interacts with the development of the entire craniofacial complex. Abnormalities of tooth development are common, with tooth agenesis being the most common developmental anomaly in humans. We performed a genome-wide association study of time to first tooth eruption and number of teeth at one year in 4,564 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966) and 1,518 individuals from the Avon Longitudinal Study of Parents and Children (ALSPAC). We identified 5 loci at P<5×10−8, and 5 with suggestive association (P<5×10−6). The loci included several genes with links to tooth and other organ development (KCNJ2, EDA, HOXB2, RAD51L1, IGF2BP1, HMGA2, MSRB3). Genes at four of the identified loci are implicated in the development of cancer. A variant within the HOXB gene cluster associated with occlusion defects requiring orthodontic treatment by age 31 years.

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Newton-Cheh C, Johnson T, Gateva V, Tobin MD, Bochud M, Coin L, Najjar SS, Zhao JH, Heath SC, Eyheramendy S, Papadakis K, Voight BF, Scott LJ, Zhang F, Farrall M, Tanaka T, Wallace C, Chambers JC, Khaw K-T, Nilsson P, van der Harst P, Polidoro S, Grobbee DE, Onland-Moret NC, Bots ML, Wain LV, Elliott KS, Teumer A, Luan J, Lucas G, Kuusisto J, Burton PR, Hadley D, McArdle WL, Brown M, Dominiczak A, Newhouse SJ, Samani NJ, Webster J, Zeggini E, Beckmann JS, Bergmann S, Lim N, Song K, Vollenweider P, Waeber G, Waterworth DM, Yuan X, Groop L, Orho-Melander M, Allione A, Di Gregorio A, Guarrera S, Panico S, Ricceri F, Romanazzi V, Sacerdote C, Vineis P, Barroso I, Sandhu MS, Luben RN, Crawford GJ, Jousilahti P, Perola M, Boehnke M, Bonnycastle LL, Collins FS, Jackson AU, Mohlke KL, Stringham HM, Valle TT, Willer CJ, Bergman RN, Morken MA, Doering A, Gieger C, Illig T, Meitinger T, Org E, Pfeufer A, Wichmann HE, Kathiresan S, Marrugat J, O'Donnell CJ, Schwartz SM, Siscovick DS, Subirana I, Freimer NB, Hartikainen A-L, McCarthy MI, O'Reilly PF, Peltonen L, Pouta A, de Jong PE, Snieder H, van Gilst WH, Clarke R, Goel A, Hamsten A, Peden JF, Seedorf U, Syvanen A-C, Tognoni G, Lakatta EG, Sanna S, Scheet P, Schlessinger D, Scuteri A, Doerr M, Ernst F, Felix SB, Homuth G, Lorbeer R, Reffelmann T, Rettig R, Voelker U, Galan P, Gut IG, Hercberg S, Lathrop GM, Zelenika D, Deloukas P, Soranzo N, Williams FM, Zhai G, Salomaa V, Laakso M, Elosua R, Forouhi NG, Volzke H, Uiterwaal CS, van der Schouw YT, Numans ME, Matullo G, Navis G, Berglund G, Bingham SA, Kooner JS, Connell JM, Bandinelli S, Ferrucci L, Watkins H, Spector TD, Tuomilehto J, Altshuler D, Strachan DP, Laan M, Meneton P, Wareham NJ, Uda M, Jarvelin M-R, Mooser V, Melander O, Loos RJF, Elliott P, Abecasis GR, Caulfield M, Munroe PBet al., 2009, Genome-wide association study identifies eight loci associated with blood pressure, Nature Genetics, Vol: 41, Pages: 666-676, ISSN: 1061-4036

Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10−24), CYP1A2 (P = 1 × 10−23), FGF5 (P = 1 × 10−21), SH2B3 (P = 3 × 10−18), MTHFR (P = 2 × 10−13), c10orf107 (P = 1 × 10−9), ZNF652 (P = 5 × 10−9) and PLCD3 (P = 1 × 10−8) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

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Sovio U, Bennett AJ, Millwood IY, Molitor J, O'Reilly PF, Timpson NJ, Kaakinen M, Laitinen J, Haukka J, Pillas D, Tzoulaki I, Molitor J, Hoggart C, Coin LJM, Whittaker J, Pouta A, Hartikainen A-L, Freimer NB, Widen E, Peltonen L, Elliott P, McCarthy MI, Jarvelin M-Ret al., 2009, Genetic Determinants of Height Growth Assessed Longitudinally from Infancy to Adulthood in the Northern Finland Birth Cohort 1966, PLOS Genetics, Vol: 5, ISSN: 1553-7390

Recent genome-wide association (GWA) studies have identified dozens of common variants associated with adult height. However, it is unknown how these variants influence height growth during childhood. We derived peak height velocity in infancy (PHV1) and puberty (PHV2) and timing of pubertal height growth spurt from parametric growth curves fitted to longitudinal height growth data to test their association with known height variants. The study consisted of N = 3,538 singletons from the prospective Northern Finland Birth Cohort 1966 with genotype data and frequent height measurements (on average 20 measurements per person) from 0–20 years. Twenty-six of the 48 variants tested associated with adult height (p<0.05, adjusted for sex and principal components) in this sample, all in the same direction as in previous GWA scans. Seven SNPs in or near the genes HHIP, DLEU7, UQCC, SF3B4/SV2A, LCORL, and HIST1H1D associated with PHV1 and five SNPs in or near SOCS2, SF3B4/SV2A, C17orf67, CABLES1, and DOT1L with PHV2 (p<0.05). We formally tested variants for interaction with age (infancy versus puberty) and found biologically meaningful evidence for an age-dependent effect for the SNP in SOCS2 (p = 0.0030) and for the SNP in HHIP (p = 0.045). We did not have similar prior evidence for the association between height variants and timing of pubertal height growth spurt as we had for PHVs, and none of the associations were statistically significant after correction for multiple testing. The fact that in this sample, less than half of the variants associated with adult height had a measurable effect on PHV1 or PHV2 is likely to reflect limited power to detect these associations in this dataset. Our study is the first genetic association analysis on longitudinal height growth in a prospective cohort from birth to adulthood and gives grounding for future research on the genetic regulation of human height during different periods of growth.

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Chadeau-Hyam M, Hoggart CJ, O'Reilly PF, Whittaker JC, De Iorio M, Balding DJet al., 2008, Fregene: Simulation of realistic sequence-level data in populations and ascertained samples, BMC BIOINFORMATICS, Vol: 9, ISSN: 1471-2105

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O'Reilly PF, Birney E, Balding DJ, 2008, Confounding between recombination and selection, and the Ped/Pop method for detecting selection, GENOME RESEARCH, Vol: 18, Pages: 1304-1313, ISSN: 1088-9051

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• Citations: 44