Genetic variation in MYLIP is associated with lipid, thyroid, liver, and hematologic traits in women

Abstract Despite the established role of MYLIP in lipid regulation, its contribution to cardiovascular disease (CVD) susceptibility has not been fully elucidated, and sex-specific effects in women remain unclear. We aimed to investigate whether genetic variation in MYLIP is associated with cardiovascular disease (CVD) risk, cardiometabolic traits, and female-specific risk factors in women. We analyzed 46,071 women from the Trøndelag Health Study (HUNT) and 220,429 women from the UK Biobank (UKB). Genetic variants in MYLIP were tested for association with CVD outcomes, biomarkers and risk factors at FDR < 0.05. No significant associations were observed between MYLIP variants and CVD outcomes after multiple testing correction, although suggestive associations were observed for dilated and hypertrophic cardiomyopathy, myocardial infarction, stroke, coronary artery disease, hypertension, as well as hyperthyroidism and hypothyroidism. MYLIP variants were associated with 17 traits in HUNT; 10 of 11 available phenotypes replicated in UKB, including lipid traits (LDL cholesterol, cholesterol, triglycerides), thyroid-stimulating hormone, liver enzymes (ASAT, ALAT, albumin), and hematologic markers (eosinophils, lymphocytes, nucleated red blood cells). MYLIP shows robust associations with lipid, liver, hematologic, and thyroid traits in women. Despite no direct CVD association, the results highlight MYLIP ’s pleiotropic role in metabolic pathways relevant to cardiovascular health in women.