Estimating disease heritability from complex pedigrees allowing for ascertainment and covariates

TY - JOUR

T1 - Estimating disease heritability from complex pedigrees allowing for ascertainment and covariates

AU - Speed, Doug

AU - Evans, David M

PY - 2024/4

Y1 - 2024/4

N2 - 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.

AB - 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.

KW - GWAS

KW - UK Biobank

KW - complex traits

KW - diseases

KW - heritability

KW - liability

KW - Genome-Wide Association Study

KW - Phenotype

KW - Pedigree

KW - Humans

KW - Models, Genetic

KW - Polymorphism, Single Nucleotide

UR - http://www.scopus.com/inward/record.url?scp=85188969496&partnerID=8YFLogxK

U2 - 10.1016/j.ajhg.2024.02.010

DO - 10.1016/j.ajhg.2024.02.010

M3 - Journal article

C2 - 38490208

SN - 0002-9297

VL - 111

SP - 680

EP - 690

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 4

ER -