Journal article
Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices
Nature communications, Vol.12(1), pp.2182-2182
04/12/2021
DOI: 10.1038/s41467-021-22339-1
PMCID: PMC8042019
PMID: 33846329
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
), 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
), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10
). 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.
Details
- Title: Subtitle
- Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices
- Creators
- Pradeep Natarajan - Harvard Medical SchoolAkhil Pampana - Broad InstituteSarah E Graham - University of MichiganSanni E Ruotsalainen - University of HelsinkiJames A Perry - University of Maryland, BaltimorePaul S de Vries - The University of Texas Health Science Center at HoustonJai G Broome - University of WashingtonJames P Pirruccello - Harvard Medical SchoolMichael C Honigberg - Harvard Medical SchoolKrishna Aragam - Harvard Medical SchoolBrooke Wolford - University of MichiganJennifer A Brody - University of WashingtonLucinda Antonacci-Fulton - Washington University in St. LouisMoscati Arden - The Charles Bronfman Institute for Personalized Medicine, Ichan School of Medicine at Mount Sinai, New York, NY, USAStella Aslibekyan - University of Alabama at BirminghamThemistocles L Assimes - VA Palo Alto Health Care SystemChristie M Ballantyne - Houston MethodistLawrence F Bielak - University of MichiganJoshua C Bis - University of WashingtonBrian E Cade - Brigham and Women's HospitalRon Do - The Charles Bronfman Institute for Personalized Medicine, Ichan School of Medicine at Mount Sinai, New York, NY, USAHarsha Doddapaneni - Baylor College of MedicineLeslie S Emery - University of WashingtonYi-Jen Hung - Tri-Service General Hospital Songshan BranchMarguerite R Irvin - University of Alabama at BirminghamAlyna T Khan - University of WashingtonLeslie Lange - University of Colorado Anschutz Medical CampusJiwon Lee - Brigham and Women's HospitalRozenn N Lemaitre - University of WashingtonLisa W Martin - George Washington UniversityGinger Metcalf - Baylor College of MedicineMay E Montasser - University of Maryland, BaltimoreJee-Young Moon - Albert Einstein College of MedicineDonna Muzny - Baylor College of MedicineJeffrey R O'Connell - University of Maryland, BaltimoreNicholette D Palmer - Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USAJuan M Peralta - Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USAPatricia A Peyser - University of MichiganAdrienne M Stilp - University of WashingtonMichael Tsai - University of MinnesotaFei Fei Wang - University of WashingtonDaniel E Weeks - University of PittsburghLisa R Yanek - Johns Hopkins University School of MedicineJames G Wilson - University of Mississippi Medical CenterGoncalo Abecasis - University of MichiganDonna K Arnett - University of KentuckyLewis C Becker - Johns Hopkins University School of MedicineJohn Blangero - Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USAEric Boerwinkle - Baylor College of MedicineDonald W Bowden - Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USAYi-Cheng Chang - National Taiwan University HospitalYii-Der I Chen - Harbor–UCLA Medical CenterWon Jung Choi - Macrogen (South Korea)Adolfo Correa - University of Mississippi Medical CenterJoanne E Curran - Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USAMark J Daly - Harvard Medical SchoolSusan K Dutcher - Washington University in St. LouisPatrick T Ellinor - Massachusetts General HospitalMyriam Fornage - The University of Texas Health Science Center at HoustonBarry I Freedman - Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-, Salem, NC, USAStacey Gabriel - Broad InstituteSoren Germer - New York Genome CenterRichard A Gibbs - Baylor College of MedicineJiang He - Tulane UniversityKristian Hveem - Norwegian University of Science and TechnologyGail P Jarvik - University of WashingtonRobert C Kaplan - Fred Hutch Cancer CenterSharon L R Kardia - University of MichiganEimear Kenny - The Charles Bronfman Institute for Personalized Medicine, Ichan School of Medicine at Mount Sinai, New York, NY, USARyan W Kim - Macrogen (South Korea)Charles Kooperberg - Fred Hutch Cancer CenterCathy C Laurie - University of WashingtonSeonwook Lee - Macrogen (South Korea)Don M Lloyd-Jones - Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USARuth J F Loos - Child Health and Development InstituteSteven A Lubitz - Massachusetts General HospitalRasika A Mathias - Johns Hopkins University School of MedicineKarine A Viaud Martinez - Illumina Laboratory Services, Illumina inc., San Diego, CA, USAStephen T McGarvey - Brown UniversityBraxton D Mitchell - Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, MD, USADeborah A Nickerson - University of WashingtonKari E North - University of North Carolina at Chapel HillAarno Palotie - Harvard Medical SchoolCheol Joo Park - Macrogen (South Korea)Bruce M Psaty - University of WashingtonD C Rao - Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USASusan Redline - Brigham and Women's HospitalAlexander P Reiner - Fred Hutch Cancer CenterDaekwan Seo - Macrogen (South Korea)Jeong-Sun Seo - Macrogen (South Korea)Albert V Smith - Icelandic Heart AssociationRussell P Tracy - University of VermontRamachandran S Vasan - Framingham Heart StudySekar Kathiresan - Verve Therapeutics (United States)L Adrienne Cupples - Boston UniversityJerome I Rotter - Harbor–UCLA Medical CenterAlanna C Morrison - The University of Texas Health Science Center at HoustonStephen S Rich - University of VirginiaSamuli Ripatti - University of HelsinkiCristen Willer - University of MichiganGina M Peloso - Boston UniversityNHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
- Contributors
- Karin Hoth (Contributor) - University of Iowa, Psychiatry
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.12(1), pp.2182-2182
- DOI
- 10.1038/s41467-021-22339-1
- PMID
- 33846329
- PMCID
- PMC8042019
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Grant note
- K01 HL135405 / NHLBI NIH HHS R01 HL120393 / NHLBI NIH HHS K01 AG059898 / NIA NIH HHS R01 HL148565 / NHLBI NIH HHS K01 HL125751 / NHLBI NIH HHS R35 HL135824 / NHLBI NIH HHS R01 HL148050 / NHLBI NIH HHS R01 HL139731 / NHLBI NIH HHS R03 HL154284 / NHLBI NIH HHS R01 HL109946 / NHLBI NIH HHS R01 HL105756 / NHLBI NIH HHS P30 DK072488 / NIDDK NIH HHS R01 HL142711 / NHLBI NIH HHS T32 HG000040 / NHGRI NIH HHS R03 HL141439 / NHLBI NIH HHS K08 HL140203 / NHLBI NIH HHS R35 HL135818 / NHLBI NIH HHS T32 HL007208 / NHLBI NIH HHS R01 HL117626 / NHLBI NIH HHS
- Language
- English
- Date published
- 04/12/2021
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984293757302771
Metrics
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