title: Common SNPs explain a large proportion of the heritability for human height.
abstract: SNPs discovered by genome-wide association studies (GWASs) account for only a small fraction of the genetic variation of complex traits in human populations. Where is the remaining heritability? We estimated the proportion of variance for human height explained by 294,831 SNPs genotyped on 3,925 unrelated individuals using a linear model analysis, and validated the estimation method with simulations based on the observed genotype data. We show that 45% of variance can be explained by considering all SNPs simultaneously. Thus, most of the heritability is not missing but has not previously been detected because the individual effects are too small to pass stringent significance tests. We provide evidence that the remaining heritability is due to incomplete linkage disequilibrium between causal variants and genotyped SNPs, exacerbated by causal variants having lower minor allele frequency than the SNPs explored to date.
authors.affiliation: Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.forename: Beben
authors.initials: B
authors.lastname: Benyamin
authors.forename: Brian P
authors.initials: BP
authors.lastname: McEvoy
authors.forename: Scott
authors.initials: S
authors.lastname: Gordon
authors.forename: Anjali K
authors.initials: AK
authors.lastname: Henders
authors.forename: Dale R
authors.initials: DR
authors.lastname: Nyholt
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Madden
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Heath
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.forename: Michael E
authors.initials: ME
authors.lastname: Goddard
authors.forename: Peter M
authors.initials: PM
authors.lastname: Visscher
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D001827:Body Height / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult