Journal
STATISTICAL APPLICATIONS IN GENETICS AND MOLECULAR BIOLOGY
Volume 16, Issue 4, Pages 259-273Publisher
WALTER DE GRUYTER GMBH
DOI: 10.1515/sagmb-2016-0076
Keywords
meta-analysis; proportions of variance; quadratic forms; variance components
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Funding
- NHLBI [HHSN268201300005C]
- National Heart, Lung, and Blood Institute (NHLBI) [N01-HC65233]
- University of Miami [N01-HC65234]
- Albert Einstein College of Medicine [N01-HC65235]
- Northwestern University [N01-HC65236]
- San Diego State University [N01-HC65237]
- HCHS/SOL
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Heritability is the proportion of phenotypic variance in a population that is attributable to individual genotypes. Heritability is considered an important measure in both evolutionary biology and in medicine, and is routinely estimated and reported in genetic epidemiology studies. In population-based genome-wide association studies (GWAS), mixed models are used to estimate variance components, from which a heritability estimate is obtained. The estimated heritability is the proportion of the model's total variance that is due to the genetic relatedness matrix (kinship measured from genotypes). Current practice is to use bootstrapping, which is slow, or normal asymptotic approximation to estimate the precision of the heritability estimate; however, this approximation fails to hold near the boundaries of the parameter space or when the sample size is small. In this paper we propose to estimate variance components via a Haseman-Elston regression, find the asymptotic distribution of the variance components and proportions of variance, and use them to construct confidence intervals (CIs). Our method is further developed to obtain unbiased variance components estimators and construct CIs by meta-analyzing information from multiple studies. We demonstrate our approach on data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).
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