Genetically Proxied Diurnal Preference, Sleep Timing, and Ri
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Morning diurnal preference is associated with a reduced risk of major depressive disorder (MDD). This JAMA Psychiatry study suggests that sleep timing patterns are a risk factor for major depressive disorder.

The objective was to examine the association of genetically proxied morning diurnal preference with depression risk using Mendelian randomization.

This 2-sample mendelian randomization study used summary-level genetic associations with diurnal preference and MDD. Up to 340 genetic loci associated with diurnal preference in a meta-analysis were considered as genetic proxies for diurnal preference. The effect size of these variants was scaled using genetic associations with accelerometer-based measurement of sleep midpoint.

A total of 697828 individuals were in the UK Biobank and 23andMe cohorts; 85502 in the UK Biobank had measurements of the sleep midpoint. A further 170756 individuals with MDD and 329443 control participants were in the Psychiatric Genomics Consortium and UK Biobank data.

--Genetically proxied earlier diurnal preference was associated with a 23% lower risk of depression. This association was similar when restricting the analysis to individuals with MDD as stringently defined by the Psychiatric Genomics Consortium but not statistically significant when defined by hospital-based billing codes in the UK Biobank.

--Sensitivity analyses examining potential bias due to pleiotropy or reverse causality showed similar findings.

The results of this mendelian randomization study support a protective association of earlier diurnal preference with the risk of MDD and provide estimates contextualized to an objective sleep timing measure.