Genome-wide association study investigating short and long sleep duration: a cross-population meta-analysis

Isabelle Austin-Zimmerman; Daniel F. Levey; Olga Giannakopoulou; Joseph D. Deak; Marco Galimberti; Hang Zhou; Spiros Denaxas; Haritz Irizar; Karoline B. Kuchenbaecker; Andrew McQuillin; the Million Veteran Program; John Concato; Daniel J. Buysse; J. Michael Gaziano; Daniel J. Gottlieb; Renato A Polimanti; Murray B. Stein; Elvira Bramon; Joel E. Gelernter

doi:10.1101/2022.09.09.22279703

Genetic & Genomic MedicinemedRxivSep 9, 2022

Preprint

Genome-wide association study investigating short and long sleep duration: a cross-population meta-analysis

Isabelle Austin-Zimmerman iD, Daniel F. Levey iD, Olga Giannakopoulou iD, Joseph D. Deak iD, Marco Galimberti iD, Hang Zhou iD, Spiros Denaxas iD, Haritz Irizar iD, Karoline B. Kuchenbaecker iD, Andrew McQuillin iD, the Million Veteran Program, John Concato iD, Daniel J. Buysse iD, J. Michael Gaziano iD, Daniel J. Gottlieb iD, Renato A Polimanti iD, Murray B. Stein iD, Elvira Bramon iD, Joel E. Gelernter iD

Abstract

Sleep duration has been linked to a wide range of negative health outcomes and to reduced life expectancy. We conducted genome-wide association studies of short ([≤]5 hours) and long ([≥]10 hours) sleep duration in adults of European, African, East Asian, and admixed-American ancestry from UK Biobank and the Million Veteran Program. In a cross-population meta-analysis we identified 84 independent loci for short sleep and 1 for long sleep. We estimated SNP-based heritability for both sleep traits in each ancestry based on population derived linkage disequilibrium (LD) scores using cov-LDSC. We identified positive genetic correlation between short and long sleep traits (rg = 0.16{+/-}0.04; P=0.0002), as well as similar patterns of genetic correlation with other psychiatric and cardiometabolic phenotypes. Mendelian randomisation revealed a directional causal relationship between short sleep and depression, and a bidirectional causal relationship between long sleep and depression.

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