Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices
AffiliationUniversity of Arizona
MetadataShow full item record
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).
RightsCopyright © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
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).
NoteOpen access journal
VersionFinal published version
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.
- Association of Genetic Variants Related to Gluteofemoral vs Abdominal Fat Distribution With Type 2 Diabetes, Coronary Disease, and Cardiovascular Risk Factors.
- Authors: Lotta LA, Wittemans LBL, Zuber V, Stewart ID, Sharp SJ, Luan J, Day FR, Li C, Bowker N, Cai L, De Lucia Rolfe E, Khaw KT, Perry JRB, O'Rahilly S, Scott RA, Savage DB, Burgess S, Wareham NJ, Langenberg C
- Issue date: 2018 Dec 25
- Genetic Association of Waist-to-Hip Ratio With Cardiometabolic Traits, Type 2 Diabetes, and Coronary Heart Disease.
- Authors: Emdin CA, Khera AV, Natarajan P, Klarin D, Zekavat SM, Hsiao AJ, Kathiresan S
- Issue date: 2017 Feb 14
- Effects of SNPs at newly identified lipids loci on blood lipid levels and risk of coronary heart disease in Chinese Han population: a case control study.
- Authors: Zhuang K, Zhang W, Zhang X, Wu F, Cheng L
- Issue date: 2011 Aug
- Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus: A Mendelian Randomization Analysis.
- 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
- Association of apolipoprotein E gene polymorphisms with blood lipids and their interaction with dietary factors.
- Authors: Shatwan IM, Winther KH, Ellahi B, Elwood P, Ben-Shlomo Y, Givens I, Rayman MP, Lovegrove JA, Vimaleswaran KS
- Issue date: 2018 Apr 30