Assessment of <i>MTNR1B</i> Type 2 Diabetes Genetic Risk Modification by Shift Work and Morningness-Eveningness Preference in the UK Biobank.

Abstract

Night shift work, behavioral rhythms, and the common <i>MTNR1B</i> risk single nucleotide polymorphism (SNP), rs10830963, associate with type 2 diabetes; however, whether they exert joint effects to exacerbate type 2 diabetes risk is unknown. Among employed participants of European ancestry in the UK Biobank (<i>N</i> = 189,488), we aimed to test the cross-sectional independent associations and joint interaction effects of these risk factors on odds of type 2 diabetes (<i>n</i> = 5,042 cases) and HbA_1c levels (<i>n</i> = 175,156). Current shift work, definite morning or evening preference, and <i>MTNR1B</i> rs10830963 risk allele associated with type 2 diabetes and HbA_1c levels. The effect of rs10830963 was not modified by shift work schedules. While marginal evidence of interaction between self-reported morningness-eveningness preference and rs10830963 on risk of type 2 diabetes was seen, this interaction did not persist when analysis was expanded to include all participants regardless of employment status and when accelerometer-derived sleep midpoint was used as an objective measure of morningness-eveningness preference. Our findings suggest that <i>MTNR1B</i> risk allele carriers who carry out shift work or have more extreme morningness-eveningness preference may not have enhanced risk of type 2 diabetes.