The ‘heritability’ of a phenotype measures the proportion of trait variance due to genetic factors in a population. In the past 50 years, studies with monozygotic and dizygotic twins have estimated heritability for 17,804 traits;1 thus twin studies are popular for estimating heritability. Researchers are often interested in estimating heritability for non-normally distributed outcomes such as binary, counts, skewed or heavy-tailed continuous traits. In these settings, the traditional normal ACE model (NACE) and Falconer's method can produce poor coverage of the true heritability. Therefore, we propose a robust generalized estimating equations (GEE2) framework for estimating the heritability of non-normally distributed outcomes. The traditional NACE and Falconer's method are derived within this unified GEE2 framework, which additionally provides robust standard errors. Although the traditional Falconer's method cannot adjust for covariates, the corresponding ‘GEE2-Falconer’ can incorporate mean and variance-level covariate effects (e.g. let heritability vary by sex or age). Given a non-normally distributed outcome, the GEE2 models are shown to attain better coverage of the true heritability compared to traditional methods. Finally, a scenario is demonstrated where NACE produces biased estimates of heritability while Falconer remains unbiased. Therefore, we recommend GEE2-Falconer for estimating the heritability of non-normally distributed outcomes in twin studies.
Bibliographical noteFunding Information:
This research was supported by the NIH grant R01DA033958 (PI: Saonli Basu) and NIH grant T32GM108557 (PI: Wei Pan).
information National Institute of Drug Abuse, R01DA033958This research was supported by the NIH grant R01DA033958 (PI: Saonli Basu) and NIH grant T32GM108557 (PI: Wei Pan).
© 2020 John Wiley & Sons, Ltd.
- generalized estimating equations
- twin studies
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural