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Sex differences in LDL-C control and race-specific genetic heritability in the All of Us Research Program

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Abstract

Cardiovascular diseases (CVDs) have been the primary source of mortality among women and men in the United States since 1921. Despite prior research demonstrating sexually dimorphic symptom presentation of CVD, women remain underdiagnosed and undertreated for CVDs. Low-density lipoprotein cholesterol (LDL-C) is a well-established and modifiable risk factor for CVDs. Here, I use genotype and phenotype data from the All of Us Research Program (AoU) to examine (a) if LDL-C measurements differ between cisgender women and cisgender men, (b) if the efficacy of statin treatment differs between these groups, (c) if there is a sex-specific difference in LDL-C measurements over age, (d) if there is a sex-specific difference in genetic variants associated with LDL-C measurements, (e) if there is a sex-specific difference in genetic effect, and (f) if heritability differs among or between groups. Based on my analysis of AoU data, I found that the median LDL-C measurements of women are consistently higher than men's and that this difference persists across all age strata and becomes most apparent in middle age. In addition, women are treated with statins at a lower rate than their male counterparts, and they are less effective. Genetic variants associated with LDL-C measurements differ between women and men, as do their effect size. Finally, I found that heritability differs between sex, age, racial identity, and treatment groups. My findings indicate that current clinical intervals of LDL-C and pharmaceutical-based LDL-C modification approaches may not be equally appropriate for cisgender women and cisgender men.

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2025-09-03

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LDL cholesteral; LDL-C; Cardiovascular disease; Population genetrics; Racial Disparities

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Government Document

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Attribution-NonCommercial-NoDerivatives 4.0 International

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dissertation or thesis

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