Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-04-12

AUTHORS

Pradeep Natarajan, Akhil Pampana, Sarah E. Graham, Sanni E. Ruotsalainen, James A. Perry, Paul S. de Vries, Jai G. Broome, James P. Pirruccello, Michael C. Honigberg, Krishna Aragam, Brooke Wolford, Jennifer A. Brody, Lucinda Antonacci-Fulton, Moscati Arden, Stella Aslibekyan, Themistocles L. Assimes, Christie M. Ballantyne, Lawrence F. Bielak, Joshua C. Bis, Brian E. Cade, Ron Do, Harsha Doddapaneni, Leslie S. Emery, Yi-Jen Hung, Marguerite R. Irvin, Alyna T. Khan, Leslie Lange, Jiwon Lee, Rozenn N. Lemaitre, Lisa W. Martin, Ginger Metcalf, May E. Montasser, Jee-Young Moon, Donna Muzny, Jeffrey R. O’Connell, Nicholette D. Palmer, Juan M. Peralta, Patricia A. Peyser, Adrienne M. Stilp, Michael Tsai, Fei Fei Wang, Daniel E. Weeks, Lisa R. Yanek, James G. Wilson, Goncalo Abecasis, Donna K. Arnett, Lewis C. Becker, John Blangero, Eric Boerwinkle, Donald W. Bowden, Yi-Cheng Chang, Yii-Der I. Chen, Won Jung Choi, Adolfo Correa, Joanne E. Curran, Mark J. Daly, Susan K. Dutcher, Patrick T. Ellinor, Myriam Fornage, Barry I. Freedman, Stacey Gabriel, Soren Germer, Richard A. Gibbs, Jiang He, Kristian Hveem, Gail P. Jarvik, Robert C. Kaplan, Sharon L. R. Kardia, Eimear Kenny, Ryan W. Kim, Charles Kooperberg, Cathy C. Laurie, Seonwook Lee, Don M. Lloyd-Jones, Ruth J. F. Loos, Steven A. Lubitz, Rasika A. Mathias, Karine A. Viaud Martinez, Stephen T. McGarvey, Braxton D. Mitchell, Deborah A. Nickerson, Kari E. North, Aarno Palotie, Cheol Joo Park, Bruce M. Psaty, D. C. Rao, Susan Redline, Alexander P. Reiner, Daekwan Seo, Jeong-Sun Seo, Albert V. Smith, Russell P. Tracy, Ramachandran S. Vasan, Sekar Kathiresan, L. Adrienne Cupples, Jerome I. Rotter, Alanna C. Morrison, Stephen S. Rich, Samuli Ripatti, Cristen Willer, Gina M. Peloso

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. More... »

PAGES

2182

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  • Journal

    TITLE

    Nature Communications

    ISSUE

    1

    VOLUME

    12

    Author Affiliations

  • Department of Medicine, Harvard Medical School, Boston, MA, USA
  • Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA
  • Department of Internal Medicine: Cardiology, University of Michigan, Ann Arbor, MI, USA
  • Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
  • University of Maryland School of Medicine, Division of Endocrinology, Diabetes and Nutrition and Program for Personalized and Genomic Medicine, Baltimore, MD, USA
  • Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA
  • Department of Biostatistics, University of Washington, Seattle, WA, USA
  • Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA
  • Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA
  • Department of Genetics, Washington University in St. Louis, St. Louis, MO, USA
  • The Charles Bronfman Institute for Personalized Medicine, Ichan School of Medicine at Mount Sinai, New York, NY, USA
  • Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA
  • VA Palo Alto Health Care System, Palo Alto, CA, USA
  • Houston Methodist Debakey Heart and Vascular Center, Houston, TX, USA
  • Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA
  • Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
  • Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA
  • Division of Endocrine and Metabolism, Tri-Service General Hospital Songshan branch, Taipei, Taiwan
  • Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
  • Division of Cardiology, George Washington University School of Medicine and Healthcare Sciences, Washington, DC, USA
  • Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA
  • Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA
  • Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA
  • Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
  • Departments of Human Genetics and Biostatistics, University of Pittsburgh, Pittsburgh, Pittsburgh, PA, USA
  • Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
  • Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA
  • Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA
  • Deans office, School of Public Health, University of Kentucky, Lexington, KY, USA
  • Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
  • The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA
  • Psomagen. Inc. (formerly Macrogen USA), Rockville, MD, USA
  • Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA
  • Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
  • Cardiac Arrhythmia Service and Cardiovascular Research Center Massachusetts General Hospital, Boston, MA, USA
  • Institute of Molecular Medicine, the University of Texas Health Science Center at Houston, Houston, TX, USA
  • Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-, Salem, NC, USA
  • Genomics Platform, Broad Institute of Harvard and MIT, Cambridge, MA, USA
  • New York Genome Center, New York, NY, USA
  • Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
  • Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, and Tulane University Translational Science Institute, Tulane University, New Orleans, LA, USA
  • K. G. Jebsen Center for Genetic Epidemiology, Dept of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
  • Departments of Medicine (Medical Genetics) and Genome Sciences, University of Washington, Seattle, WA, USA
  • Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  • Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
  • The Mindich Child Health and Development Institute, Ichan School of Medicine at Mount Sinai, New York, NY, USA
  • Illumina Laboratory Services, Illumina inc., San Diego, CA, USA
  • Department of Epidemiology and International Health Institute, Brown University, Providence, RI, USA
  • Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, MD, USA
  • University of Washington Center for Mendelian Genomics, Seattle, WA, USA
  • Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
  • Departments of Epidemiology and Health Services, University of Washington, Seattle, WA, USA
  • Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA
  • The Icelandic Heart Association, Kopavogur, Iceland
  • Departments of Pathology & Laboratory Medicine and Biochemistry, Larrner College of Medicine, University of Vermont, Colchester, VT, USA
  • NHLBI Framingham Heart Study, Framingham, MA, USA
  • Verve Therapeutics, Cambridge, MA, USA
  • Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
  • Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA
  • Department of Public Health, Faculty of Medicine, University of Helsinki, Helsinki, Finland
  • Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-021-22339-1

    DOI

    http://dx.doi.org/10.1038/s41467-021-22339-1

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1137142075

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/33846329


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