生活方式和遗传风险与英国生物库中肥胖及相关慢性疾病的关联：一项前瞻性队列研究。

Associations of Lifestyle and Genetic Risks with Obesity and Related Chronic Diseases in the UK Biobank: A Prospective Cohort Study.

机构信息

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, United States.

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, United States; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.

出版信息

Am J Clin Nutr. 2024 Jun;119(6):1514-1522. doi: 10.1016/j.ajcnut.2024.04.025. Epub 2024 Apr 25.

DOI:10.1016/j.ajcnut.2024.04.025

PMID:38677521

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11251215/

Abstract

BACKGROUND

Interplay between lifestyle risk scores (LRSs) and genetic risk scores (GRSs) on obesity and related chronic diseases are underinvestigated and necessary for understanding obesity causes and developing prevention strategies.

OBJECTIVES

This study aimed to investigate independent and joint associations and interactions of LRS and GRS with obesity prevalence and risks of diabetes, cardiovascular disease (CVD), and obesity-related cancer.

METHODS

In this cohort study of 444,957 UK Biobank participants [age: 56.5 ± 8.1 y; BMI (in kg/m): 27.4 ± 4.7], LRS included physical activity, dietary score, sedentary behavior, sleep duration, and smoking (range: 0-20, each factor had 5 levels). GRS was calculated based on 941 genetic variants related to BMI. Both scores were categorized into quintiles. Obesity (n = 106,301) was defined as baseline BMI ≥30. Incident diabetes (n = 16,311), CVD (n = 18,076), and obesity-related cancer (n = 17,325) were ascertained through linkage to registries over a median of 12-y follow-up.

RESULTS

The LRS and GRS were independently positively associated with all outcomes. Additive interactions of LRS and GRS were observed for all outcomes (P < 0.021). Comparing the top with bottom LRS quintile, prevalence differences (95% CIs) for obesity were 17.8% (15.9%, 19.7%) in the top GRS quintile and 10.7% (8.3%, 13.1%) in the bottom GRS quintile; for diabetes, CVD, and obesity-related cancer, incidence rate differences associated with per SD increase in LRS were greater in the top than that in the bottom GRS quintile. Participants from top quintiles of both LRS and GRS had 6.16-fold, 3.81-fold, 1.56-fold, and 1.44-fold higher odds/risks of obesity, diabetes, CVD, and obesity-related cancer, respectively, than those from bottom quintiles of both scores.

CONCLUSIONS

Higher LRS was associated with higher obesity prevalence and risks of related chronic diseases regardless of GRS, highlighting the broad benefits of healthy lifestyles. Additive gene-lifestyle interactions emphasize the public health importance of lifestyle interventions among people with high genetic risks.

摘要

背景

生活方式风险评分（LRS）与遗传风险评分（GRS）在肥胖症和相关慢性疾病方面的相互作用研究较少，而了解肥胖症的病因和制定预防策略则需要对其进行研究。

目的

本研究旨在探讨 LRS 和 GRS 与肥胖症患病率以及糖尿病、心血管疾病（CVD）和肥胖相关癌症风险的独立和联合关联及相互作用。

方法

在这项针对 444957 名英国生物银行参与者的队列研究中[年龄：56.5±8.1 岁；体重指数（BMI）：27.4±4.7kg/m²]，LRS 包括身体活动、饮食评分、久坐行为、睡眠时间和吸烟情况（范围：0-20，每个因素有 5 个水平）。GRS 是基于 941 个与 BMI 相关的遗传变异计算得出的。两个评分均分为五组。肥胖症（n=106301）的定义为基线 BMI≥30kg/m²。通过与登记处的链接，在中位 12 年的随访期间确定了糖尿病（n=16311）、CVD（n=18076）和肥胖相关癌症（n=17325）的发病情况。

结果

LRS 和 GRS 均与所有结局独立呈正相关。LRS 和 GRS 存在相加交互作用（P<0.021）。与 LRS 最低五分位数相比，LRS 最高五分位数中肥胖症的患病率差异（95%CI）为 17.8%（15.9%，19.7%），GRS 最高五分位数中为 10.7%（8.3%，13.1%）；对于糖尿病、CVD 和肥胖相关癌症，LRS 每增加一个标准差，与疾病相关的发病率差异在 GRS 最高五分位数中大于在 GRS 最低五分位数中。来自 LRS 和 GRS 最高五分位数的参与者发生肥胖症、糖尿病、CVD 和肥胖相关癌症的几率/风险分别比来自 LRS 和 GRS 最低五分位数的参与者高 6.16 倍、3.81 倍、1.56 倍和 1.44 倍。