Department of Epidemiology, University of North Carolina at Chapel Hill, 123 West Franklin Street, Suite 410, CB# 8050, Chapel Hill, NC, 27516, USA.
Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Curr Diab Rep. 2018 Nov 19;18(12):145. doi: 10.1007/s11892-018-1107-0.
The prevalence of obesity continues to rise, fueling a global public health crisis characterized by dramatic increases in type 2 diabetes, cardiovascular disease, and many cancers. In the USA, several minority populations, who bear much of the obesity burden (47% in African Americans and Hispanic/Latinos, compared to 38% in European descent groups), are particularly at risk of downstream chronic disease. Compounding these disparities, most genome-wide association studies (GWAS)-including those of obesity-have largely been conducted in populations of European or East Asian ancestry. In fact, analysis of the GWAS Catalog found that while the proportion of participants of non-European or non-Asian descent had risen from 4% in 2009 to 19% in 2016, African-ancestry participants are still just 3% of GWAS, Hispanic/Latinos are < 0.5%, and other ancestries are < 0.3% or not represented at all. This review summarizes recent developments in obesity genomics in US minority populations, with the goal of reducing obesity health disparities and improving public health programs and access to precision medicine.
GWAS of populations with the highest burden of obesity are essential to narrow candidate variants for functional follow-up, to identify additional ancestry-specific variants that contribute to individual genetic susceptibility, and to advance both public health and precision medicine approaches to obesity. Given the global public health burden posed by obesity and downstream chronic conditions which disproportionately affect non-European populations, GWAS of obesity-related traits in diverse populations is essential to (1) locate causal variants in GWAS-identified regions through fine mapping, (2) identify variants which influence obesity across ancestries through generalization, and (3) discover novel ancestry-specific variants which may be low frequency in European populations but common in other groups. Recent efforts to expand obesity genomic studies to understudied and underserved populations, including AAAGC, PAGE, and HISLA, are working to reduce obesity health disparities, improve public health, and bring the promise of precision medicine to all.
肥胖的流行率持续上升，引发了一场全球公共健康危机，其特征是 2 型糖尿病、心血管疾病和多种癌症的发病率显著上升。在美国，几种少数族裔人群（非裔美国人和西班牙裔/拉丁裔人群的肥胖负担占 47%，而欧洲血统人群的肥胖负担占 38%）特别面临着下游慢性疾病的风险。使这些差异更加复杂的是，大多数全基因组关联研究（GWAS）——包括肥胖相关的 GWAS——主要在欧洲或东亚血统的人群中进行。事实上，GWAS 目录的分析发现，尽管非欧洲或非亚洲血统的参与者比例从 2009 年的 4%上升到 2016 年的 19%，但非洲血统的参与者在 GWAS 中仍仅占 3%，西班牙裔/拉丁裔占<0.5%，其他血统的参与者占<0.3%或根本没有代表性。本综述总结了美国少数族裔人群中肥胖基因组学的最新进展，旨在减少肥胖相关的健康差距，改善公共卫生计划和获得精准医学的机会。
对肥胖负担最重的人群进行 GWAS 对于缩小候选变异的功能研究、确定导致个体遗传易感性的额外特定于种族的变异以及推进肥胖的公共卫生和精准医学方法都至关重要。鉴于肥胖及其下游慢性疾病给非欧洲人群带来的全球公共卫生负担，在不同人群中进行肥胖相关特征的 GWAS 对于（1）通过精细定位找到 GWAS 鉴定区域中的因果变异，（2）通过推广确定影响不同种族肥胖的变异，以及（3）发现可能在欧洲人群中频率较低但在其他人群中较常见的新的特定于种族的变异都至关重要。最近扩大肥胖基因组研究的努力，包括 AAAGC、PAGE 和 HISLA 等，旨在减少肥胖相关的健康差距，改善公共卫生，并为所有人带来精准医学的希望。
