Association between clock genes polygenic risk score for depression and obesity in a population with high burden of obesity

Abstract

Background: Circadian rhythms disruption causes clustering of metabolic disorders and depression. The comorbidity of depression and obesity is common and could be attributable to shared genetic background. We aimed to examine the association between clock genes polygenic risk score (PRS) for depression and obesity among Qatari adults. The interaction between PRS and lifestyle factors was also examined. Method: This cross-sectional study was conducted among 6,000 Qatari adults who participated in the Qatar Biobank Study. A polygenic risk scores (PRS) was constructed based on 185 single nucleotide polymorphisms (SNPs) within 18 clock genes. Dietary patterns were constructed using factor analysis based on food frequency intake. The association between exposure variables including clock genes PRS, lifestyle factors, and obesity was assessed by multivariable logistic regression models. Results: The mean age of the participants was 40.2 (13.0). The prevalence of obesity was 42.9%. A positive association between clock genes PRS and obesity was found. After adjusting for sociodemographic and lifestyle factors, across quartiles of PRS, the odds ratio (95%CI) for obesity were 1.00, 1.24, 1.19, 1.26 (95%CI 1.08–1.39), respectively. There was a borderline significant interaction between PRS and a mixed dietary pattern in relation to obesity (p for interaction 0.072). The association between PRS and obesity was only observed among those with a high intake of mixed dietary pattern. No statistically significant interactions between PRS with smoking, physical activity and other dietary patterns were found. However, the association between PRS and obesity was only observed among non-smokers, those with moderate physical activity, a low intake of sweet/fast food pattern, and high intake of modern breakfast dietary pattern. Conclusion: Clock genes PRS is positively associated with obesity and interacts with dietary pattern.