How to estimate heritability: a guide for genetic epidemiologists. (25th November 2022)

• Record Type: Journal Article
• Authors: Barry, Ciarrah-Jane S; Walker, Venexia M; Cheesman, Rosa; Davey Smith, George; Morris, Tim T; Davies, Neil M
• Is Part Of: International journal of epidemiology. Volume 52:Number 2(2023)
• Page Start: 624
• Page End: 632
• Publication Date: 2022-11-25
• Subjects: Human genetics -- epidemiologic methods -- heritability -- twin study -- human genome -- genome-wide association study; Epidemiology -- Periodicals; 614.4
• DOI: 10.1093/ije/dyac224
• Languages: English
• ISSNs: 0300-5771

Abstract

Abstract: Traditionally, heritability has been estimated using family-based methods such as twin studies. Advancements in molecular genomics have facilitated the development of methods that use large samples of (unrelated or related) genotyped individuals. Here, we provide an overview of common methods applied in genetic epidemiology to estimate heritability, i.e. the proportion of phenotypic variation explained by genetic variation. We provide a guide to key genetic concepts required to understand heritability estimation methods from family-based designs (twin and family studies), genomic designs based on unrelated individuals [linkage disequilibrium score regression, genomic relatedness restricted maximum-likelihood (GREML) estimation] and family-based genomic designs (sibling regression, GREML-kinship, trio-genome-wide complex trait analysis, maternal-genome-wide complex trait analysis, relatedness disequilibrium regression). We describe how heritability is estimated for each method and the assumptions underlying its estimation, and discuss the implications when these assumptions are not met. We further discuss the benefits and limitations of estimating heritability within samples of unrelated individuals compared with samples of related individuals. Overall, this article is intended to help the reader determine the circumstances when each method would be appropriate and why.