Ying Jiacheng, Ye Ding, Luo Peiyang, Liu Bin, Chen Weiwei, Qian Yu, Sun Xiaohui, Mao Yingying
The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China.
School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Clin Nutr. 2024 Jun;43(6):1544-1550. doi: 10.1016/j.clnu.2024.05.016. Epub 2024 May 9.
Few prospective studies have investigated the joint effect of lifestyle factors and genetic susceptibility on the risk of irritable bowel syndrome (IBS). This study aims to evaluate the associations of lifestyle and genetic factors with incident IBS in the UK Biobank. We analyzed data from 481,057 participants (54% female) without prevalent IBS at enrollment in the UK Biobank. An overall healthy lifestyle was defined using six modifiable lifestyle factors, including smoking, body mass index (BMI), sleep duration, diet, physical activity, and alcohol consumption, and hence categorized into 'favorable', 'intermediate', and 'unfavorable' lifestyles. A Cox proportional hazard model was used to investigate the association between a healthy lifestyle and incident IBS. Furthermore, we constructed a polygenic risk score (PRS) for IBS and assessed whether lifestyle modified the effect of genetics on the development of IBS. During a median follow-up of 12.1 years, 8645 incident IBS were ascertained. Specifically, among the six modifiable lifestyle factors, adequate sleep demonstrates the greatest protective effect (hazard ratio [HR]: 0.72, 95% CI: 0.69,0.75) against IBS. Compared with a favorable lifestyle, an unfavorable lifestyle was associated with a 56% (95% CI: 46%-67%) increased risk of IBS (P = 8.99 × 10). The risk of incident IBS was 12% (95% CI: 4%-21%) higher among those at high genetic risk compared with those at low genetic risk (P = 0.005). When considering the joint effect of lifestyle and genetic susceptibility, the HR nearly doubled among individuals with high genetic risk and unfavorable lifestyle (HR: 1.80; 95% CI:1.51-2.15; P = 3.50 × 10) compared to those with low genetic risk and favorable lifestyle. No multiplicative or addictive interaction was observed between lifestyle and genetics. The findings from this study indicated that lifestyle and genetic factors were independently associated with the risk of incident IBS. All these results implicated a possible clinical strategy of lowering the incidence of IBS by advocating a healthy lifestyle.
很少有前瞻性研究调查生活方式因素和遗传易感性对肠易激综合征（IBS）风险的联合影响。本研究旨在评估英国生物银行中生活方式和遗传因素与新发IBS的关联。我们分析了英国生物银行中481,057名入组时无IBS病史参与者（54%为女性）的数据。使用包括吸烟、体重指数（BMI）、睡眠时间、饮食、体育活动和饮酒在内的六个可改变生活方式因素来定义总体健康生活方式，并据此分为“良好”、“中等”和“不良”生活方式。采用Cox比例风险模型研究健康生活方式与新发IBS之间的关联。此外，我们构建了IBS的多基因风险评分（PRS），并评估生活方式是否改变了遗传因素对IBS发生发展的影响。在中位随访12.1年期间，确定了8645例新发IBS病例。具体而言，在六个可改变生活方式因素中，充足睡眠对IBS的保护作用最大（风险比[HR]：0.72，95%置信区间：0.69，0.75）。与良好生活方式相比，不良生活方式与IBS风险增加56%（95%置信区间：46%-67%）相关（P = 8.99×10）。高遗传风险者新发IBS的风险比低遗传风险者高12%（95%置信区间：4%-21%）（P = 0.005）。当考虑生活方式和遗传易感性的联合影响时，与低遗传风险和良好生活方式者相比，高遗传风险和不良生活方式者的HR几乎翻倍（HR：1.80；95%置信区间：1.51-2.15；P = 3.50×10）。未观察到生活方式与遗传因素之间的相乘或相加相互作用。本研究结果表明，生活方式和遗传因素与新发IBS风险独立相关。所有这些结果都暗示了一种通过倡导健康生活方式来降低IBS发病率的可能临床策略。
