Evaluating causal associations between chronotype and fatty acids and between fatty acids and type 2 diabetes: A Mendelian randomization study

Background and aimsPreference for activity in the morning or evening (chronotype) may impact type 2 diabetes (T2D) risk factors. Our objective was to use Mendelian randomization (MR) to evaluate whether there are causal links between chronotype and one potential T2D risk factor, total fatty acids (TOTFA), and between TOTFA and T2D.Methods and resultsWe estimated the causal effect of: 1) morning chronotype on TOTFA; and 2) higher TOTFA on T2D. We found that: a) morning compared to evening chronotype was associated with lower TOTFA levels (inverse-weighted variance (IVW) estimate −0.21; 95% CI −0.38, −0.03; raw P = 0.02; FDR-corrected P 0.04) and b) elevated TOTFA levels were protective against T2D (IVW estimate −0.23; 95% CI −0.41, −0.05; raw P = 0.01; FDR-corrected P = 0.03). Based on this finding, we further hypothesized that healthy fats would show a similar pattern and performed MR of a) morning chronotype on omega-3 (Omega-3), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids; and b) MR of each of these fat types on T2D. We observed the same mediating-type pattern for chronotype, MUFA, and T2D as we had for chronotype, TOTFA, and T2D, and morning chronotype was associated with lower Omega-3.ConclusionOur findings provide suggestive, new information about relationships among chronotype, TOTFA, and T2D and about chronotype as a factor influencing Omega-3, MUFA, and TOTFA levels. In addition, we validated previous knowledge about MUFA and T2D. Morning chronotypes may predispose towards lower levels of TOTFA and some healthy fats, whereas higher levels of TOTFA and MUFA may protect against T2D.