Abstract
Genetic factors increase the risk of depression, but the extent to which this can be offset by modifiable lifestyle factors is unknown. We investigated whether a combination of healthy lifestyles is associated with lower risk of depression regardless of genetic risk. Data were obtained from the UK Biobank and consisted of 339,767 participants (37–73 years old) without depression between 2006 and 2010. Genetic risk was categorized as low, intermediate, or high according to polygenic risk score for depression. A combination of healthy lifestyles factors—including no current smoking, regular physical activity, a healthy diet, moderate alcohol intake and a body mass index <30 kg/m2—was categorized into favorable, intermediate, and unfavorable lifestyles. The risk of depression was 22% higher among those at high genetic risk compared with those at low genetic risk (HR = 1.22, 95% CI: 1.14–1.30). Participants with high genetic risk and unfavorable lifestyle had a more than two-fold risk of incident depression compared with low genetic risk and favorable lifestyle (HR = 2.18, 95% CI: 1.84–2.58). There was no significant interaction between genetic risk and lifestyle factors (P for interaction = 0.69). Among participants at high genetic risk, a favorable lifestyle was associated with nearly 50% lower relative risk of depression than an unfavorable lifestyle (HR = 0.51, 95% CI: 0.43–0.60). We concluded that genetic and lifestyle factors were independently associated with risk of incident depression. Adherence to healthy lifestyles may lower the risk of depression regardless of genetic risk.
Highlights
Depression is a major cause of death in the UK population, and incidence rate has been on the rise, as 19.7% UK people aged 16 years and older showed symptoms of depression or anxiety in 20141
The analyses were adjusted for age, sex, qualifications, socioeconomic status and first 10 principal components of ancestry, individual lifestyle factor was adjusted for each other. In this large-scale prospective study, we found that genetic risk and lifestyle factors were independently associated with the risk of depression
These findings provide evidence for the necessity of a combination of healthy lifestyle factors in preventing depression and reinforce the considerable potential of primary prevention
Summary
Depression is a major cause of death in the UK population, and incidence rate has been on the rise, as 19.7% UK people aged 16 years and older showed symptoms of depression or anxiety in 20141. Depression is a complex disease that is affected by both genetic and environmental factors. The effect of genetic predisposition on the risk of depression has been examined in the previous studies[3,4]. A metaanalysis showed that the heritability for depression was 37% (95% CI: 31–42%), and data from family studies have. These single nucleotide polymorphisms (SNPs) provided quantitative measures of genetic susceptibilities and may be predictive of the incidence of depression[9]. Lifestyle is a common and crucial modifiable risk factor for depression. A large number of evidence has established that many individual lifestyle factors—such as nonsmoking[10], a healthy diet[11], physical activity[12], moderate alcohol intake[13], and a healthy weight14—are associated with decreased risk of depression. As for other diseases, recent studies have shown that adherence to a combined healthy
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