Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices
In: Nature Communications, Jg. 12 (2021), Heft 1
Online
academicJournal
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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.
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Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices
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Autor/in / Beteiligte Person: | 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 |
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Zeitschrift: | Nature Communications, Jg. 12 (2021), Heft 1 |
Veröffentlichung: | eScholarship, University of California, 2021 |
Medientyp: | academicJournal |
Umfang: | 2182 |
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