TY - JOUR
T1 - Detection of gene-environment interaction in pedigree data using genome-wide genotypes
AU - Nivard, Michel G.
AU - Middeldorp, Christel M.
AU - Lubke, Gitta
AU - Hottenga, Jouke-Jan
AU - Abdellaoui, Abdel
AU - Boomsma, Dorret I.
AU - Dolan, Conor V.
N1 - Funding Information: This study was supported by the following: Genetic influences on stability and change in psychopathology from childhood to young adulthood (ZonMW 91210020); Genetics of Mental Illness (European Research Council ERC-230374); Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL, 184.021.007); Community's Seventh Framework Program (FP7/2007-2013); ENGAGE (HEALTH-F4-2007-201413); the Avera Institute, Sioux Falls, South Dakota (USA) and Grand Opportunity grants 1RC2 MH089951 and 1RC2 MH089995. GL was supported by the National Institute on Drug Abuse Grant No. DA018673. MGN is supported by a Royal Netherlands Academy of Science Professor Award (PAH/6635) to DIB. We thank Karin Verweij for critically reviewing the manuscript. Publisher Copyright: © 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Heritability may be estimated using phenotypic data collected in relatives or in distantly related individuals using genome-wide single nucleotide polymorphism (SNP) data. We combined these approaches by re-parameterizing the model proposed by Zaitlen et al and extended this model to include moderation of (total and SNP-based) genetic and environmental variance components by a measured moderator. By means of data simulation, we demonstrated that the type 1 error rates of the proposed test are correct and parameter estimates are accurate. As an application, we considered the moderation by age or year of birth of variance components associated with body mass index (BMI), height, attention problems (AP), and symptoms of anxiety and depression. The genetic variance of BMI was found to increase with age, but the environmental variance displayed a greater increase with age, resulting in a proportional decrease of the heritability of BMI. Environmental variance of height increased with year of birth. The environmental variance of AP increased with age. These results illustrate the assessment of moderation of environmental and genetic effects, when estimating heritability from combined SNP and family data. The assessment of moderation of genetic and environmental variance will enhance our understanding of the genetic architecture of complex traits.
AB - Heritability may be estimated using phenotypic data collected in relatives or in distantly related individuals using genome-wide single nucleotide polymorphism (SNP) data. We combined these approaches by re-parameterizing the model proposed by Zaitlen et al and extended this model to include moderation of (total and SNP-based) genetic and environmental variance components by a measured moderator. By means of data simulation, we demonstrated that the type 1 error rates of the proposed test are correct and parameter estimates are accurate. As an application, we considered the moderation by age or year of birth of variance components associated with body mass index (BMI), height, attention problems (AP), and symptoms of anxiety and depression. The genetic variance of BMI was found to increase with age, but the environmental variance displayed a greater increase with age, resulting in a proportional decrease of the heritability of BMI. Environmental variance of height increased with year of birth. The environmental variance of AP increased with age. These results illustrate the assessment of moderation of environmental and genetic effects, when estimating heritability from combined SNP and family data. The assessment of moderation of genetic and environmental variance will enhance our understanding of the genetic architecture of complex traits.
UR - http://www.scopus.com/inward/record.url?scp=84979236480&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/ejhg.2016.88
DO - https://doi.org/10.1038/ejhg.2016.88
M3 - Article
C2 - 27436263
SN - 1018-4813
VL - 24
SP - 1803
EP - 1809
JO - European journal of human genetics
JF - European journal of human genetics
IS - 12
ER -