Influence of autozygosity on common disease risk across the phenotypic spectrum

23andMe Research Team, Genes & Health Research Team

    Research output: Contribution to journalArticleAcademicpeer-review

    2 Citations (Scopus)

    Abstract

    Autozygosity is associated with rare Mendelian disorders and clinically relevant quantitative traits. We investigated associations between the fraction of the genome in runs of homozygosity (FROH) and common diseases in Genes & Health (n = 23,978 British South Asians), UK Biobank (n = 397,184), and 23andMe. We show that restricting analysis to offspring of first cousins is an effective way of reducing confounding due to social/environmental correlates of FROH. Within this group in G&H+UK Biobank, we found experiment-wide significant associations between FROH and twelve common diseases. We replicated associations with type 2 diabetes (T2D) and post-traumatic stress disorder via within-sibling analysis in 23andMe (median n = 480,282). We estimated that autozygosity due to consanguinity accounts for 5%–18% of T2D cases among British Pakistanis. Our work highlights the possibility of widespread non-additive genetic effects on common diseases and has important implications for global populations with high rates of consanguinity.

    Original languageEnglish
    Pages (from-to)4514-4527.e14
    Number of pages29
    JournalCell
    Volume186
    Issue number21
    Early online date26 Sept 2023
    DOIs
    Publication statusPublished - 12 Oct 2023

    Keywords

    • autozygosity
    • common diseases
    • consanguinity
    • diverse cohorts
    • medical genetics
    • recessive

    Cite this