Genomic control for association studies.
Bernie Devlin,Kathryn Roeder +1 more
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TLDR
The performance of the genomic control method is quite good for plausible effects of liability genes, which bodes well for future genetic analyses of complex disorders.Abstract:
A dense set of single nucleotide polymorphisms (SNP) covering the genome and an efficient method to assess SNP genotypes are expected to be available in the near future. An outstanding question is how to use these technologies efficiently to identify genes affecting liability to complex disorders. To achieve this goal, we propose a statistical method that has several optimal properties: It can be used with case control data and yet, like family-based designs, controls for population heterogeneity; it is insensitive to the usual violations of model assumptions, such as cases failing to be strictly independent; and, by using Bayesian outlier methods, it circumvents the need for Bonferroni correction for multiple tests, leading to better performance in many settings while still constraining risk for false positives. The performance of our genomic control method is quite good for plausible effects of liability genes, which bodes well for future genetic analyses of complex disorders.read more
Citations
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Journal ArticleDOI
LDL-cholesterol concentrations: a genome-wide association study
Manjinder S. Sandhu,Dawn M. Waterworth,Sally L Debenham,Eleanor Wheeler,Konstantinos A. Papadakis,Jing Hua Zhao,Kijoung Song,Xin H. Yuan,Toby Johnson,Toby Johnson,Sofie Ashford,Michael Inouye,Robert Luben,Matthew A. Sims,David Hadley,Wendy L. McArdle,Philip J. Barter,Y. Antero Kesäniemi,Robert W. Mahley,Ruth McPherson,Scott M. Grundy,Sheila Bingham,Kay-Tee Khaw,Ruth J. F. Loos,Gérard Waeber,Inês Barroso,David P. Strachan,Panagiotis Deloukas,Peter Vollenweider,Nicholas J. Wareham,Vincent Mooser +30 more
TL;DR: SNPs rs599839 and rs646776 both explained around 1% of the variation in circulating LDL-cholesterol concentrations and were associated with about 15% of an SD change in LDL cholesterol per allele, assuming an SD of 1 mmol/L.
Journal ArticleDOI
Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma
Gudmar Thorleifsson,G. Bragi Walters,Alex W. Hewitt,Alex W. Hewitt,Gisli Masson,Agnar Helgason,Agnar Helgason,Andrew T. DeWan,Asgeir Sigurdsson,Adalbjorg Jonasdottir,Sigurjon A. Gudjonsson,Kristinn P. Magnusson,Hreinn Stefansson,Dennis S.C. Lam,Pancy O. S. Tam,Gudrun J Gudmundsdottir,Laura Southgate,Kathryn P. Burdon,Maria Soffia Gottfredsdottir,Micheala A. Aldred,Paul Mitchell,David St Clair,David A. Collier,David A. Collier,Nelson L.S. Tang,Orn Sveinsson,Stuart MacGregor,Nicholas G. Martin,Angela J. Cree,Jane Gibson,Alex MacLeod,Aby Jacob,Sarah Ennis,Terri L. Young,Juliana C.N. Chan,W Karwatowski,Christopher J Hammond,Kristjan Thordarson,Mingzhi Zhang,Claes Wadelius,Andrew J. Lotery,Richard C. Trembath,Chi Pui Pang,Josephine Hoh,Jamie E Craig,Augustine Kong,David A. Mackey,David A. Mackey,David A. Mackey,Fridbert Jonasson,Unnur Thorsteinsdottir,Unnur Thorsteinsdottir,Kari Stefansson,Kari Stefansson +53 more
TL;DR: The risk variant identified here is located close to CAV1 and CAV2, both of which are expressed in the trabecular meshwork and retinal ganglion cells that are involved in the pathogenesis of POAG.
Journal ArticleDOI
The landscape of recombination in African Americans
Anjali Gupta Hinch,Arti Tandon,Arti Tandon,Nick Patterson,Yunli Song,Nadin Rohland,Nadin Rohland,Cameron D. Palmer,Cameron D. Palmer,Gary K. Chen,Kai Wang,Kai Wang,Sarah G. Buxbaum,Ermeg L. Akylbekova,Ermeg L. Akylbekova,Melinda C. Aldrich,Christine B. Ambrosone,Christopher I. Amos,Elisa V. Bandera,Sonja I. Berndt,Leslie Bernstein,William J. Blot,Cathryn H. Bock,Eric Boerwinkle,Qiuyin Cai,Neil E. Caporaso,Graham Casey,L. Adrienne Cupples,L. Adrienne Cupples,Sandra L. Deming,W. Ryan Diver,Jasmin Divers,Myriam Fornage,Elizabeth M. Gillanders,Joseph T. Glessner,Curtis C. Harris,Jennifer J. Hu,Sue A. Ingles,William B. Isaacs,Esther M. John,Esther M. John,W. H. Linda Kao,Brendan J. Keating,Rick A. Kittles,Laurence N. Kolonel,Emma K. Larkin,Loic Le Marchand,Lorna H. McNeill,Robert C. Millikan,Adam B. Murphy,Solomon K. Musani,Christine Neslund-Dudas,Sarah J. Nyante,George J. Papanicolaou,Michael F. Press,Bruce M. Psaty,Alexander P. Reiner,Stephen S. Rich,Jorge L. Rodriguez-Gil,Jerome I. Rotter,Benjamin A. Rybicki,Ann G. Schwartz,Lisa B. Signorello,Margaret R. Spitz,Sara S. Strom,Michael J. Thun,Margaret A. Tucker,Zhaoming Wang,John K. Wiencke,John S. Witte,Margaret Wrensch,Xifeng Wu,Yuko Yamamura,Krista A. Zanetti,Wei Zheng,Regina G. Ziegler,Xiaofeng Zhu,Susan Redline,Joel N. Hirschhorn,Joel N. Hirschhorn,Brian E. Henderson,Herman A. Taylor,Herman A. Taylor,Herman A. Taylor,Alkes L. Price,Hakon Hakonarson,Stephen J. Chanock,Christopher A. Haiman,James G. Wilson,David Reich,David Reich,Simon Myers +91 more
TL;DR: This work builds a genetic map measuring the probability of crossing over at each position in the genome, based on about 2.1 million crossovers in 30,000 unrelated African Americans, and identifies about 2,500 recombination hotspots that are active in people of West African ancestry but nearly inactive in Europeans.
Journal ArticleDOI
A genome-wide association meta-analysis identifies new childhood obesity loci
Jonathan P. Bradfield,H R Taal,Nicholas J. Timpson,André Scherag,C. Lecoeur,Nicole M. Warrington,Elina Hyppönen,Claus Holst,Beatriz Valcarcel,Elisabeth Thiering,Rany M. Salem,Fredrick R. Schumacher,Diana L. Cousminer,Pma Sleiman,Jianhua Zhao,Robert I. Berkowitz,Karani Santhanakrishnan Vimaleswaran,Ivonne Jarick,Craig E. Pennell,David M. Evans,B. St Pourcain,Diane J. Berry,Dennis O. Mook-Kanamori,Albert Hofman,Fernando Rivadeneira,André G. Uitterlinden,C M van Duijn,Rjp van der Valk,J. C. de Jongste,D. S. Postma,Dorret I. Boomsma,W. J. Gauderman,Mohamed T. Hassanein,Cecilia M. Lindgren,Reedik Mägi,Reedik Mägi,Cag Boreham,Charlotte E. Neville,Luis A. Moreno,Paul Elliott,A Pouta,A.-L. Hartikainen,Mingyao Li,Olli T. Raitakari,Terho Lehtimäki,Johan G. Eriksson,Aarno Palotie,Jean Dallongeville,Shikta Das,Panagiotis Deloukas,George McMahon,Susan M. Ring,John P. Kemp,Jessica L. Buxton,Aif Blakemore,Mariona Bustamante,Mònica Guxens,Joel N. Hirschhorn,Matthew W. Gillman,Eskil Kreiner-Møller,Hans Bisgaard,Frank D. Gilliland,Joachim Heinrich,Eleanor Wheeler,Inês Barroso,Inês Barroso,Stephen O'Rahilly,Aline Meirhaeghe,Tia Sorensen,Chris Power,Lyle J. Palmer,Anke Hinney,E. Widen,I. S. Farooqi,Mark I. McCarthy,Philippe Froguel,Philippe Froguel,David Meyre,David Meyre,Johannes Hebebrand,M-R Jarvelin,Vwv Jaddoe,George Davey Smith,Hakon Hakonarson,Sfa Grant +84 more
TL;DR: A North American, Australian and European collaborative meta-analysis of 14 studies consisting of 5,530 cases and 8,318 controls of European ancestry observed two loci that yielded genome-wide significant combined P values near OLFM4 at 13q14 and within HOXB5 at 17q21, which yielded directionally consistent associations.
Journal ArticleDOI
Accounting for ancestry: population substructure and genome-wide association studies
TL;DR: It is suggested that it will be important to explore results in homogeneous population subsets as the authors seek to define the extent to which genomic variation influences complex phenotypes.
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