Widespread recessive effects on common diseases in a cohort of 44,000 British Pakistanis and Bangladeshis with high autozygosity

Teng Hiang Heng; Klaudia Walter; Qin Huang; Juha M Karjalainen; Mark J. Daly; Henrike Heyne; Daniel Shiloh Malawsky; Georgios Kalantzis; Sarah Finer; David A. van Heel; Hilary C. Martin

doi:10.1016/j.ajhg.2025.03.020

Genetic & Genomic MedicineThe American Journal of Human GeneticsApr 29, 2025

Peer-reviewed journal article

Widespread recessive effects on common diseases in a cohort of 44,000 British Pakistanis and Bangladeshis with high autozygosity

Teng Hiang Heng iD, Klaudia Walter iD, Qin Huang iD, Juha M Karjalainen iD, Mark J. Daly iD, Henrike Heyne iD, Daniel Shiloh Malawsky iD, Georgios Kalantzis iD, Sarah Finer iD, David A. van Heel iD, Hilary C. Martin iD

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Abstract

Genetic association studies have focused on testing additive models in cohorts with European ancestry. Little is known about recessive effects on common diseases, specifically for non-European ancestry. Genes & Health is a cohort of British Pakistani and Bangladeshi individuals with elevated rates of consanguinity and endogamy, making it suitable to study recessive effects. We imputed variants into 44,190 genotyped individuals, using two imputation panels: a set of 4,982 whole-exome-sequences from within the cohort, and the TOPMed-r2 panel. We performed association testing with 898 diseases from electronic health records. We identified 185 independent loci that reached standard genome-wide significance (p View larger version (42K): org.highwire.dtl.DTLVardef@1c6e696org.highwire.dtl.DTLVardef@14c82c3org.highwire.dtl.DTLVardef@1ce563org.highwire.dtl.DTLVardef@117f6da_HPS_FORMAT_FIGEXP M_FIG C_FIG