Environmental and Genetic Influences on Low-density Lipoprotein Cholesterol Levels and Cholesterol-lowering Medication Use in Asian Americans:Findings from the All of Us Research Program

Abstract

Cardiovascular disease (CVD) remains the leading cause of death globally and in the US. Around 7% of Asian Americans have CVD, posing a significant health burden. One of the major risk factors for CVD is elevated Low-density lipoprotein (LDL) cholesterol. Although extensive research has examined LDL cholesterol and its environmental and genetic determinants in the general population, studies focused specifically on Asian Americans are limited. Statins, essential for reducing LDL cholesterol and preventing CVD, are often underused in the US, with about 40% of eligible individuals not receiving treatment. Research on racial disparities in statin use has primarily highlighted Black/African American and Hispanic American populations, leaving gaps in understanding for Asian Americans. This study aims to identify environmental and genetic factors affecting LDL cholesterol levels and assess statin use and barriers among Asian Americans. We analyzed data from self-reported Asian American adults aged 18 and older in the All of Us Research Program. Environmental factors were examined using surveys, physical measurements, and lab data. We also conducted a genome-wide association study (GWAS) to test the association between genetic markers and LDL cholesterol levels. Statin use was assessed based on the 2013 ACC/AHA (American College of Cardiology/American Heart Association) Blood Cholesterol Guideline. Our findings indicate that Asian Americans have higher LDL cholesterol levels compared to other racial/ethnic groups, with no significant lifestyle factors linked to high LDL cholesterol. GWAS analysis identified six suggestive SNPs associated with decreasing the risk of high LDL cholesterol. Among them, rs5748554 and rs6485549 were located near ZDHHC8 and DKK3, which are indirectly related to lipid metabolism. Despite eligibility, only two-thirds of Asian Americans received cholesterol-lowering medications, and statin use was 17% lower in women than in men with ASCVD (atherosclerotic cardiovascular disease), indicating a notable gender disparity. The public health significance of this study is identifying novel genetic and non-genetic risk factors for high LDL cholesterol and underutilizing lipid-lowering medication. These findings will help to understand population-specific factors affecting LDL cholesterol and inform tailored interventions for its management by improving medication adherence, ultimately leading to improved cardiovascular health in this population