Genetic Influences on Evening Preference Overlap with Those for Bipolar Disorder in a Sample of Mexican Americans and American Indians.

Abstract

Diurnal preference (e.g., being an owl or lark) has been associated with several psychiatric disorders including bipolar disorder (BP), major depressive disorder, and substance use disorders. Previous large-scale genome-wide association studies (GWAS) aimed at identifying genetic influences on diurnal preference have exclusively included subjects of European ancestry. This study examined the genetic architecture of diurnal preference in two minority samples: a young adult sample of Mexican Americans (MAs), and a family-based sample of American Indians (AIs). Typed or imputed variants from exome chip data from the MA sample and low pass whole-genome sequencing from the AI cohort were analyzed using a mixed linear model approach for association with being an owl, as defined by a usual bedtime after 23:00 hrs. Genetic risk score (GRS) profiling detected shared genetic risk between evening preference and related disorders. Four variants in KIAA1549 like (KIAA1549L), a gene previously associated with attempted suicide in bipolar patients, were suggestively associated with being an owl at p < 1.82E-05; post hoc analyses showed the top variant trending in both the MA and AI cohorts at p = 2.50E-05 and p = .030, respectively. Variants associated with BP at p < .03 from the Psychiatric Genomics Consortium nominally predicted being an owl in the MA/AI cohort at p = .012. This study provides some additional evidence that genetic risk factors for BP also confer risk for being an owl in MAs/AIs and that evening preference may be a useful endophenotype for future studies of BP.