Underestimation of heritability using a mixed model with a polygenic covariance structure in a genome-wide association study for complex traits

European Journal of Human Genetics

Volumn 22, Issue 6, 2014, Pages 851-854

  Ryoo, Hyunju ^a   Lee, Chaeyoung ^a  

^a Soongsil University   (South Korea)

Author keywords

heritability; mixed model; simulation

Indexed keywords

ALLELE; ARTICLE; DIASTOLIC BLOOD PRESSURE; GENE SEQUENCE; GENETIC ASSOCIATION; GENETIC MODEL; GENETIC VARIABILITY; HERITABILITY; HUMAN; HYPERTENSION; MAXIMUM LIKELIHOOD METHOD; MOLECULAR PHYLOGENY; PRIORITY JOURNAL; QUANTITATIVE TRAIT; SEQUENCE ANALYSIS; SINGLE NUCLEOTIDE POLYMORPHISM; SYSTOLIC BLOOD PRESSURE; VARIANCE; ALGORITHM; BIOLOGICAL MODEL; COMPUTER SIMULATION; GENETICS; GENOTYPE; MULTIFACTORIAL INHERITANCE; PHENOTYPE; PROCEDURES; QUANTITATIVE TRAIT LOCUS; REPRODUCIBILITY;

ALGORITHMS; COMPUTER SIMULATION; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; HUMANS; HYPERTENSION; MODELS, GENETIC; MULTIFACTORIAL INHERITANCE; PHENOTYPE; POLYMORPHISM, SINGLE NUCLEOTIDE; QUANTITATIVE TRAIT LOCI; REPRODUCIBILITY OF RESULTS;

EID: 84901001653     PISSN: 10184813     EISSN: 14765438     Source Type: Journal    
DOI: 10.1038/ejhg.2013.236     Document Type: Article

References (19)

1. Hindorff LA, Sethupathy P, Junkins HA et al: Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci USA 2009; 106: 9362-9367.
2. Visscher PM, Brown MA, McCarthy MI et al: Five years of GWAS discovery. Am J Hum Genet 2012; 90: 7-24.
3. Yang J, Manolio TA, Pasquale LR et al: Genome partitioning of genetic variation for complex traits using common SNPs. Nat Genet 2011; 43: 519-525.
4. Devlin B, Roeder K: Genomic control for association studies. Biometrics 1999; 55: 997-1004.
5. Price AL, Patterson NJ, Plenge RM et al: Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 2006; 38: 904-909.
6. Hoggart CJ, Parra EJ, Shriver MD et al: Control of confounding of genetic associations in stratified populations. Am J Hum Genet 2003; 72: 1492-1504.
7. Kang HM, Sul JH, Service SK et al: Variance component model to account for sample structure in genome-wide association studies. Nat Genet 2010; 42: 348-354.
8. Zhang Z, Ersoz E, Lai CQ et al: Mixed linear model approach adapted for genome-wide association studies. Nat Genet 2010; 42: 355-360.
9. Cho YS, Go MJ, Kim YJ et al: A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits. Nat Genet 2009; 41: 527-534.
10. Yang J, Lee SH, Goddard ME et al: GCTA: a tool for genome-wide complex trait analysis. Am J Hum Genet 2011; 88: 76-82.
11. Lee SH, Wray NR, Goddard ME et al: Estimating missing heritability for disease from genome-wide association studies. Am J Hum Genet 2011; 88: 294-305.
12. Girirajan S, Campbell CD, Eichler EE: Human copy number variation and complex genetic disease. Annu Rev Genet 2011; 45: 203-226.
13. Manolio TA, Collins FS, Cox NJ et al: Finding the missing heritability of complex diseases. Nature 2009; 461: 747-753.
14. Eichler EE, Flint J, Gibson G et al: Missing heritability and strategies for finding the underlying causes of complex disease. Nat Rev Genet 2010; 11: 446-450.
15. Gibson G: Rare and common variants: twenty arguments. Nat Rev Genet 2012; 13: 135-145.
16. Kindt AS, Navarro P, Semple CA et al: The genomic signature of trait-associated variants. BMC Genomics 2013; 14: 108.
17. Zuk O, Hechter E, Sunyaev SR et al: The mystery of missing heritability: genetic interactions create phantom heritability. Proc Natl Acad Sci USA 2012; 109: 1193-1198.
18. Zaitlen N, Kraft P: Heritability in the genome-wide association era. Hum Genet 2012; 131: 1655-1664.
19. Lippert C, Quon G, Kang EY et al: The benefits of selecting phenotype-specific variants for applications of mixed models in genomics. Sci Rep 2013; 3: 1815.