A multi-SNP locus-association method reveals a substantial fraction of the missing heritability

American Journal of Human Genetics

Volumn 91, Issue 5, 2012, Pages 863-871

  Ehret, Georg B ^a,b   Lamparter, David ^c,d   Hoggart, Clive J ^e   Whittaker, John C ^f   Beckmann, Jacques S ^c,g   Kutalik, Zoltán ^c,d  

^a GENEVA UNIVERSITY HOSPITALS   (Switzerland)

^b JOHNS HOPKINS UNIVERSITY   (United States)

^c UNIVERSITY OF LAUSANNE   (Switzerland)

^d SWISS INSTITUTE OF BIOINFORMATICS   (Switzerland)

^e IMPERIAL COLLEGE LONDON   (United Kingdom)

^f GLAXOSMITHKLINE   (United Kingdom)

^g LAUSANNE UNIVERSITY HOSPITAL   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ALLELE; ANTHROPOMETRY; ARTICLE; BODY MASS; GENE IDENTIFICATION; GENE LINKAGE DISEQUILIBRIUM; GENE LOCUS; GENE REPLICATION; GENETIC ASSOCIATION; HERITABILITY; HUMAN; META ANALYSIS (TOPIC); PHENOTYPE; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM; WAIST HIP RATIO;

BODY MASS INDEX; GENOME-WIDE ASSOCIATION STUDY; HUMANS; LIPIDS; PHENOTYPE; POLYMORPHISM, SINGLE NUCLEOTIDE; QUANTITATIVE TRAIT LOCI; WAIST-HIP RATIO;

EID: 84868369445     PISSN: 00029297     EISSN: 15376605     Source Type: Journal    
DOI: 10.1016/j.ajhg.2012.09.013     Document Type: Article

References (26)

1. L.A. Hindorff, P. Sethupathy, H.A. Junkins, E.M. Ramos, J.P. Mehta, F.S. Collins, and T.A. Manolio Potential etiologic and functional implications of genome-wide association loci for human diseases and traits Proc. Natl. Acad. Sci. USA 106 2009 9362 9367
2. B. Maher Personal genomes: The case of the missing heritability Nature 456 2008 18 21
3. T.A. Manolio, F.S. Collins, N.J. Cox, D.B. Goldstein, L.A. Hindorff, D.J. Hunter, M.I. McCarthy, E.M. Ramos, L.R. Cardon, and A. Chakravarti Finding the missing heritability of complex diseases Nature 461 2009 747 753
4. J. Yang, B. Benyamin, B.P. McEvoy, S. Gordon, A.K. Henders, D.R. Nyholt, P.A. Madden, A.C. Heath, N.G. Martin, and G.W. Montgomery Common SNPs explain a large proportion of the heritability for human height Nat. Genet. 42 2010 565 569
5. R.G. Walters, S. Jacquemont, A. Valsesia, A.J. de Smith, D. Martinet, J. Andersson, M. Falchi, F. Chen, J. Andrieux, and S. Lobbens A new highly penetrant form of obesity due to deletions on chromosome 16p11.2 Nature 463 2010 671 675
6. I.P. Tomlinson, L.G. Carvajal-Carmona, S.E. Dobbins, A. Tenesa, A.M. Jones, K. Howarth, C. Palles, P. Broderick, E.E. Jaeger, S. Farrington COGENT Consortium CORGI Collaborators EPICOLON Consortium Multiple common susceptibility variants near BMP pathway loci GREM1, BMP4, and BMP2 explain part of the missing heritability of colorectal cancer PLoS Genet. 7 2011 e1002105
7. M.P. Audrézet, J.M. Chen, O. Raguénès, N. Chuzhanova, K. Giteau, C. Le Maréchal, I. Quéré, D.N. Cooper, and C. Férec Genomic rearrangements in the CFTR gene: Extensive allelic heterogeneity and diverse mutational mechanisms Hum. Mutat. 23 2004 343 357
8. H. Lango Allen, K. Estrada, G. Lettre, S.I. Berndt, M.N. Weedon, F. Rivadeneira, C.J. Willer, A.U. Jackson, S. Vedantam, and S. Raychaudhuri Hundreds of variants clustered in genomic loci and biological pathways affect human height Nature 467 2010 832 838
9. E.K. Speliotes, C.J. Willer, S.I. Berndt, K.L. Monda, G. Thorleifsson, A.U. Jackson, H. Lango Allen, C.M. Lindgren, J. Luan, R. Mägi MAGIC Procardis Consortium Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index Nat. Genet. 42 2010 937 948
10. I.M. Heid, A.U. Jackson, J.C. Randall, T.W. Winkler, L. Qi, V. Steinthorsdottir, G. Thorleifsson, M.C. Zillikens, E.K. Speliotes, R. Mägi MAGIC Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution Nat. Genet. 42 2010 949 960
11. J. Yang, T. Ferreira, A.P. Morris, S.E. Medland, P.A. Madden, A.C. Heath, N.G. Martin, G.W. Montgomery, M.N. Weedon, R.J. Loos Genetic Investigation of ANthropometric Traits (GIANT) Consortium DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits Nat. Genet. 44 2012 369 375 S1-S3
12. Y. Benjamini, and Y. Hochberg Controlling the false discovery rate: A practical and powerful approach to multiple testing Journal of the Royal Statistical Society Series B (Methodological) 57 1995 289 300
13. W. Cheney, and D. Kincaid Numerical Mathematics and Computing Sixth Edition 2007 Thomson Belmont, U.S.A.
14. F.E. Harrel Regression modeling strategies: With Applications to Linear Models, Logistic Regression, and Survival Analysis First Edition 2010 Springer-Verlag New York
15. M. Firmann, V. Mayor, P.M. Vidal, M. Bochud, A. Pécoud, D. Hayoz, F. Paccaud, M. Preisig, K.S. Song, and X. Yuan The CoLaus study: A population-based study to investigate the epidemiology and genetic determinants of cardiovascular risk factors and metabolic syndrome BMC Cardiovasc. Disord. 8 2008 6
16. H. Theil Economic forecasts and policy. Contributions to economic analysis 1961 North-Holland Publishing Company Amsterdam
17. S. Sunyaev, V. Ramensky, I. Koch, W. Lathe 3rd, A.S. Kondrashov, and P. Bork Prediction of deleterious human alleles Hum. Mol. Genet. 10 2001 591 597
18. J.J. Kim, Y.M. Park, K.H. Baik, H.Y. Choi, G.S. Yang, I. Koh, J.A. Hwang, J. Lee, Y.S. Lee, and H. Rhee Exome sequencing and subsequent association studies identify five amino acid-altering variants influencing human height Hum. Genet. 131 2012 471 478
19. T.M. Teslovich, K. Musunuru, A.V. Smith, A.C. Edmondson, I.M. Stylianou, M. Koseki, J.P. Pirruccello, S. Ripatti, D.I. Chasman, and C.J. Willer Biological, clinical and population relevance of 95 loci for blood lipids Nature 466 2010 707 713
20. A.R. Wood, D.G. Hernandez, M.A. Nalls, H. Yaghootkar, J.R. Gibbs, L.W. Harries, S. Chong, M. Moore, M.N. Weedon, and J.M. Guralnik Allelic heterogeneity and more detailed analyses of known loci explain additional phenotypic variation and reveal complex patterns of association Hum. Mol. Genet. 20 2011 4082 4092
21. S. Nejentsev, J.M. Howson, N.M. Walker, J. Szeszko, S.F. Field, H.E. Stevens, P. Reynolds, M. Hardy, E. King, J. Masters Wellcome Trust Case Control Consortium Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A Nature 450 2007 887 892
22. G. Orozco, A. Hinks, S. Eyre, X. Ke, L.J. Gibbons, J. Bowes, E. Flynn, P. Martin, A.G. Wilson, D.E. Bax Wellcome Trust Case Control Consortium YEAR consortium Combined effects of three independent SNPs greatly increase the risk estimate for RA at 6q23 Hum. Mol. Genet. 18 2009 2693 2699
23. H. Hor, Z. Kutalik, Y. Dauvilliers, A. Valsesia, G.J. Lammers, C.E. Donjacour, A. Iranzo, J. Santamaria, R. Peraita Adrados, and J.L. Vicario Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy Nat. Genet. 42 2010 786 789
24. X. Wang, X. Liu, X. Sim, H. Xu, C.C. Khor, R.T. Ong, W.T. Tay, C. Suo, W.T. Poh, and D.P. Ng A statistical method for region-based meta-analysis of genome-wide association studies in genetically diverse populations Eur. J. Hum. Genet. 20 2012 469 475
25. J.K. Pritchard, and N.J. Cox The allelic architecture of human disease genes: Common disease-common variant...or not? Hum. Mol. Genet. 11 2002 2417 2423
26. J.Z. Liu, A.F. McRae, D.R. Nyholt, S.E. Medland, N.R. Wray, K.M. Brown, N.K. Hayward, G.W. Montgomery, P.M. Visscher, N.G. Martin, S. Macgregor AMFS Investigators A versatile gene-based test for genome-wide association studies Am. J. Hum. Genet. 87 2010 139 145