학술논문
Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices
Document Type
Original Paper
Author
Natarajan, Pradeep; Pampana, Akhil; Graham, Sarah E.; Ruotsalainen, Sanni E.; Perry, James A.; de Vries, Paul S.; Broome, Jai G.; Pirruccello, James P.; Honigberg, Michael C.; Aragam, Krishna; Wolford, Brooke; Brody, Jennifer A.; Antonacci-Fulton, Lucinda; Arden, Moscati; Aslibekyan, Stella; Assimes, Themistocles L.; Ballantyne, Christie M.; Bielak, Lawrence F.; Bis, Joshua C.; Cade, Brian E.; Do, Ron; Doddapaneni, Harsha; Emery, Leslie S.; Hung, Yi-Jen; Irvin, Marguerite R.; Khan, Alyna T.; Lange, Leslie; Lee, Jiwon; Lemaitre, Rozenn N.; Martin, Lisa W.; Metcalf, Ginger; Montasser, May E.; Moon, Jee-Young; Muzny, Donna; O’Connell, Jeffrey R.; Palmer, Nicholette D.; Peralta, Juan M.; Peyser, Patricia A.; Stilp, Adrienne M.; Tsai, Michael; Wang, Fei Fei; Weeks, Daniel E.; Yanek, Lisa R.; Wilson, James G.; Abecasis, Goncalo; Arnett, Donna K.; Becker, Lewis C.; Blangero, John; Boerwinkle, Eric; Bowden, Donald W.; Chang, Yi-Cheng; Chen, Yii-Der I.; Choi, Won Jung; Correa, Adolfo; Curran, Joanne E.; Daly, Mark J.; Dutcher, Susan K.; Ellinor, Patrick T.; Fornage, Myriam; Freedman, Barry I.; Gabriel, Stacey; Germer, Soren; Gibbs, Richard A.; He, Jiang; Hveem, Kristian; Jarvik, Gail P.; Kaplan, Robert C.; Kardia, Sharon L. R.; Kenny, Eimear; Kim, Ryan W.; Kooperberg, Charles; Laurie, Cathy C.; Lee, Seonwook; Lloyd-Jones, Don M.; Loos, Ruth J. F.; Lubitz, Steven A.; Mathias, Rasika A.; Martinez, Karine A. Viaud; McGarvey, Stephen T.; Mitchell, Braxton D.; Nickerson, Deborah A.; North, Kari E.; Palotie, Aarno; Park, Cheol Joo; Psaty, Bruce M.; Rao, D. C.; Redline, Susan; Reiner, Alexander P.; Seo, Daekwan; Seo, Jeong-Sun; Smith, Albert V.; Tracy, Russell P.; Vasan, Ramachandran S.; Kathiresan, Sekar; Cupples, L. Adrienne; Rotter, Jerome I.; Morrison, Alanna C.; Rich, Stephen S.; Ripatti, Samuli; Willer, Cristen; Peloso, Gina M.
Source
Nature Communications. 12(1)
Subject
Language
English
ISSN
2041-1723
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 × 10−72 ), 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.
The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.
The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.