Declining Autozygosity Over Time: An Exploration in Over 1 Million Individuals From Three Diverse Cohorts

Authors

Sarah M C Colbert
Frank R Wendt
Gita A Pathak
Drew A Helmer
Elizabeth R Hauser
Matthew C Keller
Renato Polimanti
Emma C Johnson

Publication Date

6-1-2023

Journal

American Journal of Human Genetics

DOI

10.1016/j.ajhg.2023.04.007

PMID

37178685

PMCID

PMC10257001

PubMedCentral® Posted Date

5-12-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Homozygote, Polymorphism, Single Nucleotide, Population Health, autozygosity, runs of homozygosity, FROH, panmixia

Abstract

Previous studies have hypothesized that autozygosity is decreasing over generational time. However, these studies were limited to relatively small samples (n < 11,000) lacking in diversity, which may limit the generalizability of their findings. We present data that partially support this hypothesis from three large cohorts of diverse ancestries, two from the US (All of Us, n = 82,474; the Million Veteran Program, n = 622,497) and one from the UK (UK Biobank, n = 380,899). Our results from a mixed-effect meta-analysis demonstrate an overall trend of decreasing autozygosity over generational time (meta-analyzed slope = -0.029, SE = 0.009, p = 6.03e-4). On the basis of our estimates, we would predict F