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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- Authors: Zhuang K, Zhang W, Zhang X, Wu F, Cheng L
- Issue date: 2011 Aug
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- Authors: Dale CE, Fatemifar G, Palmer TM, White J, Prieto-Merino D, Zabaneh D, Engmann JEL, Shah T, Wong A, Warren HR, McLachlan S, Trompet S, Moldovan M, Morris RW, Sofat R, Kumari M, Hyppönen E, Jefferis BJ, Gaunt TR, Ben-Shlomo Y, Zhou A, Gentry-Maharaj A, Ryan A, UCLEB Consortium; METASTROKE Consortium., Mutsert R, Noordam R, Caulfield MJ, Jukema JW, Worrall BB, Munroe PB, Menon U, Power C, Kuh D, Lawlor DA, Humphries SE, Mook-Kanamori DO, Sattar N, Kivimaki M, Price JF, Davey Smith G, Dudbridge F, Hingorani AD, Holmes MV, Casas JP
- Issue date: 2017 Jun 13
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