Estimating disease heritability from complex pedigrees allowing for ascertainment and covariates

Doug Speed*, David M Evans

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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.

Original languageEnglish
JournalAmerican Journal of Human Genetics
Volume111
Issue4
Pages (from-to)680-690
Number of pages11
ISSN0002-9297
DOIs
Publication statusPublished - Apr 2024

Keywords

  • GWAS
  • UK Biobank
  • complex traits
  • diseases
  • heritability
  • liability
  • Genome-Wide Association Study
  • Phenotype
  • Pedigree
  • Humans
  • Models, Genetic
  • Polymorphism, Single Nucleotide

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