Testing the key assumption of heritability estimates based on genome-wide genetic relatedness.

TitleTesting the key assumption of heritability estimates based on genome-wide genetic relatedness.
Publication TypeJournal Article
Year of Publication2014
AuthorsConley, DC, Siegal, ML, Domingue, BW, Harris, KMullan, McQueen, MB, Boardman, JD
JournalJ Hum Genet
Volume59
Issue6
Pagination342-5
Date Published2014 Jun
ISSN Number1435-232X
KeywordsBody Height, Body Weight, Educational Status, Gene-Environment Interaction, Genome, Human, Humans, Likelihood Functions, Models, Genetic, Phenotype, Quantitative Trait, Heritable, Urban Population
Abstract

Comparing genetic and phenotypic similarity among unrelated individuals seems a promising way to quantify the genetic component of traits while avoiding the problematic assumptions plaguing twin- and other kin-based estimates of heritability. One approach uses a Genetic Relatedness Estimation through Maximum Likelihood (GREML) model for individuals who are related at less than 0.025 to predict their phenotypic similarity by their genetic similarity. Here we test the key underlying assumption of this approach: that genetic relatedness is orthogonal to environmental similarity. Using data from the Health and Retirement Study (and two other surveys), we show two unrelated individuals may be more likely to have been reared in a similar environment (urban versus nonurban setting) if they are genetically similar. This effect is not eliminated by controls for population structure. However, when we include this environmental confound in GREML models, heritabilities do not change substantially and thus potential bias in estimates of most biological phenotypes is probably minimal.

DOI10.1038/jhg.2014.14
User Guide Notes

http://www.ncbi.nlm.nih.gov/pubmed/24599117?dopt=Abstract

Endnote Keywords

environmental confound/GREML/heritability

Endnote ID

999999

Alternate JournalJ. Hum. Genet.
Citation Key7993
PubMed ID24599117
PubMed Central IDPMC4126504
Grant ListRC4AG039029 / AG / NIA NIH HHS / United States
R01 HD060726 / HD / NICHD NIH HHS / United States
R01 HD073342 / HD / NICHD NIH HHS / United States
U01AG009740 / AG / NIA NIH HHS / United States
R24 HD050924 / HD / NICHD NIH HHS / United States
RC2AG036495 / AG / NIA NIH HHS / United States