e-Article
Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices.
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article
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 LR; Kenny, Eimear; Kim, Ryan W; Kooperberg, Charles; Laurie, Cathy C; Lee, Seonwook; Lloyd-Jones, Don M; Loos, Ruth JF; 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, DC; 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
Source
Nature communications. 12(1)
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Language
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.