A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices
Tekijät: 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; NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium; FinnGen, Peloso Gina M.
Kustantaja: NATURE RESEARCH
Julkaisuvuosi: 2021
Journal: Nature Communications
Tietokannassa oleva lehden nimi: NATURE COMMUNICATIONS
Lehden akronyymi: NAT COMMUN
Artikkelin numero: ARTN 2182
Vuosikerta: 12
Numero: 1
Sivujen määrä: 14
ISSN: 2041-1723
eISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-021-22339-1
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=8.5x10-72), 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=1.7x10-4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P=1.4x10-5). 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.
