Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices
AffiliationUniversity of Arizona
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CitationNatarajan, P., Pampana, A., Graham, S.E. et al. Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices. Nat Commun 12, 2182 (2021).
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AbstractAutosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids. © 2021, The Author(s).
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Except where otherwise noted, this item's license is described as Copyright © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License.
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