Polygenic risk score, healthy lifestyles, and risk of incident depression

Genetic factors increase the risk of depression, but the extent to which this can be offset by modifiable lifestyle factors is unknown. Researchers 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 categorised 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 categorised into favourable, 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 unfavourable lifestyle had a more than two-fold risk of incident depression compared with low genetic risk and favourable lifestyle (HR = 2.18, 95% CI: 1.84-2.58). There was no significant interaction between genetic risk and lifestyle factors. Among participants at high genetic risk, a favourable lifestyle was associated with nearly 50% lower relative risk of depression than an unfavourable lifestyle (HR = 0.51, 95% CI: 0.43-0.60).
The researchers 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.
Source: Cao Z, Yang H, Ye Y, Zhang Y, Li S, Zhao H, Wang Y. Polygenic risk score, healthy lifestyles, and risk of incident depression. Transl Psychiatry. 2021 Mar 29;11(1):189. .