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

Aug 13, 2024Journal of affective disorders

How healthy lifestyle and genetic risk relate to bipolar disorder

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Abstract

A total of 529 individuals developed bipolar disorder (BD) during a 12.9-year follow-up of 365,517 participants.

Individuals with a favorable lifestyle had a 3.28 times higher hazard ratio of developing BD compared to those with an unfavorable lifestyle.
A high polygenic risk score (PRS) was associated with a 3.20 times greater risk of BD compared to a low PRS.
Those with both a high PRS and an unfavorable lifestyle had a significantly increased risk of BD, with a hazard ratio of 6.31.
The interaction between PRS and lifestyle contributed an additional risk, with a relative excess risk of 1.74.
A favorable lifestyle may reduce the risk of developing BD, indicating potential benefit from lifestyle modifications.

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BACKGROUND: The interplay between genetic and lifestyle factors in the development of bipolar disorder (BD) remains unclear.

METHODS: 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.

RESULTS: 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).

CONCLUSIONS: 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.

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

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