Association of healthy lifestyle factors and genetic liability with bipolar disorder: Findings from the UK Biobank.

The interplay between genetic and lifestyle factors in the development of bipolar disorder (BD) remains unclear. A cohort study was carried out on 365,517 participants from the UK Biobank. Lifestyle scores, based on smoking, physical activity, diet, alcohol consumption, sedentary behavior, sleep duration, and social contact, were grouped as favorable (scores 6–7), intermediate (scores 4–5), or unfavorable (scores 0–3). The BD polygenic risk score (PRS) was also categorized into high, intermediate, and low-risk groups using PRS tertiles. Cox regression models determined hazard ratios (HRs) and 95 % confidence intervals (CIs) for BD. During the 12.9-year follow-up, 529 individuals developed BD. Comparing those with favorable lifestyles to those with unfavorable participants, the HR of developing BD was 3.28 (95 % CI, 2.76–3.89). Similarly, individuals with a high PRS had a risk of 3.20 (95 % CI, 2.83–3.63) compared to those with a low PRS. Notably, individuals with both a high PRS and an unfavorable lifestyle had a significantly higher risk of BD (HR = 6.31, 95 % CI, 4.14–9.63) compared to those with a low PRS and a favorable lifestyle. Additionally, the interaction between PRS and lifestyle contributed an additional risk, with a relative excess risk of 1.74 (95 % CI, 0.40–3.07) and an attributable proportion due to the interaction of 0.37 (95 % CI, 0.16–0.58). Our findings suggest that genetic liability for BD, measured as PRS, and lifestyle have an additive effect on the risk of developing BD. A favorable lifestyle was associated with a reduced risk of developing BD. • High polygenic risk score (PRS) and unfavorable lifestyles both increase risk of bipolar disorder (BD). • The coexistence of high PRS and unfavorable lifestyle has an additive interaction on the risk of developing BD. • Irrespective of PRS, adopting a favorable lifestyle was consistently linked to a decreased risk of BD. [ABSTRACT FROM AUTHOR]