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

Night shift work, behavioral rhythms, and the common MTNR1B 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 (N=189,488), we aimed to test the cross-sectional independent associations and joint interactions of these risk factors on odds of type 2 diabetes (n=5,042 cases) and HbA1c levels (n=175,156). Current shift work, definite morning or evening preference, and MTNR1B rs10830963 risk-allele associate with type 2 diabetes and HbA1c 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 was seen on risk of type 2 diabetes, this interaction did not persist when analysis was expanded to include all participants regardless of employment status and when using accelerometer-derived sleep-midpoint as an objective measure of morningness-eveningness preference. Our findings suggest that the MTNR1B risk-allele carriers may not have greater vulnerability to shift work or morningness-eveningness preference.