Estimating disease heritability from complex pedigrees allowing for ascertainment and covariates

Doug Speed; David M Evans

doi:10.1016/j.ajhg.2024.02.010

Estimating disease heritability from complex pedigrees allowing for ascertainment and covariates

Am J Hum Genet. 2024 Apr 4;111(4):680-690. doi: 10.1016/j.ajhg.2024.02.010. Epub 2024 Mar 14.

Authors

Doug Speed¹, David M Evans²

Affiliations

¹ Center for Quantitative Genetics and Genomics, Aarhus University, Aarhus, Denmark. Electronic address: doug@qgg.au.dk.
² Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia; Frazer Institute, University of Queensland, Brisbane, QLD, Australia; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.

PMID: 38490208
PMCID: PMC11023822 (available on 2024-10-04)
DOI: 10.1016/j.ajhg.2024.02.010

Abstract

We propose TetraHer, a method for estimating the liability heritability of binary phenotypes. TetraHer has five key features. First, it can be applied to data from complex pedigrees that contain multiple types of relationships. Second, it can correct for ascertainment of cases or controls. Third, it can accommodate covariates. Fourth, it can model the contribution of common environment. Fifth, it produces a likelihood that can be used for significance testing. We first demonstrate the validity of TetraHer on simulated data. We then use TetraHer to estimate liability heritability for 229 codes from the tenth International Classification of Diseases (ICD-10). We identify 107 codes with significant heritability (p < 0.05/229), which can be used in future analyses for investigating the genetic architecture of human diseases.

Keywords: GWAS; UK Biobank; complex traits; diseases; heritability; liability.

MeSH terms

Genome-Wide Association Study*
Humans
Models, Genetic*
Pedigree
Phenotype
Polymorphism, Single Nucleotide