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Confidence intervals for heritability via Haseman-Elston regression.

TitleConfidence intervals for heritability via Haseman-Elston regression.
Publication TypePublication
Year2017
AuthorsSofer T
JournalStat Appl Genet Mol Biol
Volume16
Issue4
Pagination259-273
Date Published2017 09 26
ISSN1544-6115
KeywordsConfidence Intervals, genome-wide association study, Genotype, Humans, Models, Genetic, Quantitative Trait, Heritable
Abstract

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).

DOI10.1515/sagmb-2016-0076
Alternate JournalStat Appl Genet Mol Biol
PubMed ID28862991
PubMed Central IDPMC5857391
Grant ListN01 HC065234 / HC / NHLBI NIH HHS / United States
HHSN268201300005C / HL / NHLBI NIH HHS / United States
N01HC65236 / HL / NHLBI NIH HHS / United States
N01HC65235 / HL / NHLBI NIH HHS / United States
N01HC65234 / HL / NHLBI NIH HHS / United States
N01 HC065233 / HC / NHLBI NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States
N01HC65237 / HL / NHLBI NIH HHS / United States
MS#: 
0554
Manuscript Lead/Corresponding Author Affiliation: 
HCHS/SOL Genetic Analysis Center - University of Washington, Seattle
ECI: 
Manuscript Affiliation: 
HCHS/SOL Genetic Analysis Center - University of Washington, Seattle
Manuscript Status: 
Published