Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices.

TitleChromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices.
Publication TypeJournal Article
Year of Publication2021
AuthorsNatarajan, P, Pampana, A, Graham, SE, Ruotsalainen, SE, Perry, JA, de Vries, PS, Broome, JG, Pirruccello, JP, Honigberg, MC, Aragam, K, Wolford, B, Brody, JA, Antonacci-Fulton, L, Arden, M, Aslibekyan, S, Assimes, TL, Ballantyne, CM, Bielak, LF, Bis, JC, Cade, BE, Do, R, Doddapaneni, H, Emery, LS, Hung, Y-J, Irvin, MR, Khan, AT, Lange, L, Lee, J, Lemaitre, RN, Martin, LW, Metcalf, G, Montasser, ME, Moon, J-Y, Muzny, DM, O'Connell, JR, Palmer, ND, Peralta, JM, Peyser, PA, Stilp, AM, Tsai, M, Wang, FFei, Weeks, DE, Yanek, LR, Wilson, JG, Abecasis, G, Arnett, DK, Becker, LC, Blangero, J, Boerwinkle, E, Bowden, DW, Chang, Y-C, Chen, Y-DI, Choi, WJung, Correa, A, Curran, JE, Daly, MJ, Dutcher, SK, Ellinor, PT, Fornage, M, Freedman, BI, Gabriel, S, Germer, S, Gibbs, RA, He, J, Hveem, K, Jarvik, GP, Kaplan, RC, Kardia, SLR, Kenny, E, Kim, RW, Kooperberg, C, Laurie, CC, Lee, S, Lloyd-Jones, DM, Loos, RJF, Lubitz, SA, Mathias, RA, Martinez, KAViaud, McGarvey, ST, Mitchell, BD, Nickerson, DA, North, KE, Palotie, A, Park, CJoo, Psaty, BM, Rao, DC, Redline, S, Reiner, AP, Seo, D, Seo, J-S, Smith, AV, Tracy, RP, Vasan, RS, Kathiresan, S, L Cupples, A, Rotter, JI, Morrison, AC, Rich, SS, Ripatti, S, Willer, C, Peloso, GM
Corporate AuthorsNHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, FinnGen
JournalNat Commun
Volume12
Issue1
Pagination2182
Date Published2021 04 12
ISSN2041-1723
KeywordsCardiometabolic Risk Factors, Chromosomes, Human, X, Eye Proteins, Female, Gene Expression Regulation, Genetic Association Studies, Genetic Loci, Genetic Predisposition to Disease, Genotype, Humans, Lipids, Male, Middle Aged, Nerve Tissue Proteins, Phenomics, Polymorphism, Single Nucleotide, Subcutaneous Tissue, Whole Genome Sequencing
Abstract

Autosomal 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), 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), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10). 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.

DOI10.1038/s41467-021-22339-1
Alternate JournalNat Commun
PubMed ID33846329
PubMed Central IDPMC8042019
Grant ListR03 HL141439 / HL / NHLBI NIH HHS / United States
R01 HL139731 / HL / NHLBI NIH HHS / United States
R35 HL135818 / HL / NHLBI NIH HHS / United States
R01 HL148050 / HL / NHLBI NIH HHS / United States
K01 HL125751 / HL / NHLBI NIH HHS / United States
R01 HL142711 / HL / NHLBI NIH HHS / United States
K01 HL135405 / HL / NHLBI NIH HHS / United States
K08 HL140203 / HL / NHLBI NIH HHS / United States
R01 HL117626 / HL / NHLBI NIH HHS / United States
R01 HL148565 / HL / NHLBI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States