Whole-genome sequencing of African Americans implicates differential genetic architecture in inflammatory bowel disease.

Black or African American / genetics Aged Aged, 80 and over Calbindin 2 / genetics Colitis, Ulcerative / genetics Crohn Disease / genetics Female Gene Frequency Genetic Predisposition to Disease Genome-Wide Association Study Humans Inflammatory Bowel Diseases / genetics Male Multifactorial Inheritance / genetics Polymorphism, Single Nucleotide / genetics Receptors, Prostaglandin E, EP4 Subtype / genetics White People / genetics Whole Genome Sequencing
CALB2 PTGER4 differential genetic architecture polygenic risk scores rare variants trans-ethnic comparative analysis understudied populations whole-genome sequencing of African Americans

Journal

American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475

Informations de publication

Date de publication:
04 03 2021
Historique:
received: 21 09 2020
accepted: 01 02 2021
pubmed: 19 2 2021
medline: 25 3 2021
entrez: 18 2 2021
Statut: ppublish

Résumé

Whether or not populations diverge with respect to the genetic contribution to risk of specific complex diseases is relevant to understanding the evolution of susceptibility and origins of health disparities. Here, we describe a large-scale whole-genome sequencing study of inflammatory bowel disease encompassing 1,774 affected individuals and 1,644 healthy control Americans with African ancestry (African Americans). Although no new loci for inflammatory bowel disease are discovered at genome-wide significance levels, we identify numerous instances of differential effect sizes in combination with divergent allele frequencies. For example, the major effect at PTGER4 fine maps to a single credible interval of 22 SNPs corresponding to one of four independent associations at the locus in European ancestry individuals but with an elevated odds ratio for Crohn disease in African Americans. A rare variant aggregate analysis implicates Ca

Identifiants

DOI: 10.1016/j.ajhg.2021.02.001 PMID: 33600772 PMC: PMC8008495
pubmed: 33600772
pii: S0002-9297(21)00043-4
doi: 10.1016/j.ajhg.2021.02.001
pmc: PMC8008495
pii:
doi:

Substances chimiques

CALB2 protein, human 0
Calbindin 2 0
PTGER4 protein, human 0
Receptors, Prostaglandin E, EP4 Subtype 0

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

431-445

Subventions

Organisme : NIDCR NIH HHS
ID : U54 DE023789
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK042086
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG008895
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK062429
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK062432
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK062429
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK062422
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK062423
Pays : United States
Organisme : NHGRI NIH HHS
ID : U54 HG003067
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK062413
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI067068
Pays : United States
Organisme : NIDDK NIH HHS
ID : P01 DK046763
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK062420
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK062431
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK087694
Pays : United States

Informations de copyright

Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

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Auteurs

Hari K Somineni (HK)

Genetics and Molecular Biology Program, Emory University, Atlanta, GA 30322, USA; Division of Pediatric Gastroenterology, Department of Pediatrics, Emory University School of Medicine & Children's Healthcare of Atlanta, Atlanta, GA 30322, USA.

Sini Nagpal (S)

Center for Integrative Genomics, Georgia Institute of Technology, Atlanta, GA 30332, USA.

Suresh Venkateswaran (S)

Division of Pediatric Gastroenterology, Department of Pediatrics, Emory University School of Medicine & Children's Healthcare of Atlanta, Atlanta, GA 30322, USA.

David J Cutler (DJ)

Department of Human Genetics, Emory University, Atlanta, GA 30322, USA.

David T Okou (DT)

Division of Pediatric Gastroenterology, Department of Pediatrics, Emory University School of Medicine & Children's Healthcare of Atlanta, Atlanta, GA 30322, USA.

Talin Haritunians (T)

F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

Claire L Simpson (CL)

Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

Ferdouse Begum (F)

Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Lisa W Datta (LW)

Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Antonio J Quiros (AJ)

Department of Pediatrics, Medical University of South Carolina, Pediatric Center for Inflammatory Bowel Disorders, Summerville, SC 29485, USA.

Jenifer Seminerio (J)

Department of Gastroenterology, Medical University of South Carolina Digestive Disease Center, Charleston, SC 29425, USA.

Emebet Mengesha (E)

F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

Jonathan S Alexander (JS)

Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USA.

Robert N Baldassano (RN)

Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

Sharon Dudley-Brown (S)

Department of Medicine, Johns Hopkins University Schools of Medicine & Nursing, Baltimore, MD 21205, USA.

Raymond K Cross (RK)

Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Themistocles Dassopoulos (T)

Baylor Scott and White Center for Inflammatory Bowel Diseases, Texas A&M University, Dallas, TX 75202, USA.

Lee A Denson (LA)

Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.

Tanvi A Dhere (TA)

Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.

Heba Iskandar (H)

Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.

Gerald W Dryden (GW)

Department of Medicine, University of Louisville, Louisville, KY 40202, USA.

Jason K Hou (JK)

Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.

Sunny Z Hussain (SZ)

Department of Pediatrics, Willis-Knighton Physician Network, Shreveport, LA 71101, USA.

Jeffrey S Hyams (JS)

Connecticut Children's Medical Center, Hartford, CT 06106, USA.

Kim L Isaacs (KL)

Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Howard Kader (H)

Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Michael D Kappelman (MD)

Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.

Jeffry Katz (J)

Case Western Reserve University, Cleveland, OH 44106, USA.

Richard Kellermayer (R)

Section of Pediatric Gastroenterology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA.

John F Kuemmerle (JF)

Division of Gastroenterology, Hepatology and Nutrition, Medical College of Virginia Campus of Virginia Commonwealth University, Richmond, VA 23284, USA.

Mark Lazarev (M)

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Ellen Li (E)

Department of Medicine, Stony Brook University School of Medicine, Stony Brook, NY 11794, USA.

Peter Mannon (P)

Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35233, USA.

Dedrick E Moulton (DE)

Vanderbilt Children's Hospital, Nashville, TN 37232, USA.

Rodney D Newberry (RD)

Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Ashish S Patel (AS)

Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Joel Pekow (J)

Department of Pediatrics, University of Chicago Comer Children's Hospital, Chicago, IL 60637, USA.

Shehzad A Saeed (SA)

Dayton Children's Hospital, Dayton, OH 45404, USA.

John F Valentine (JF)

University of Utah, Health Sciences, Salt Lake City, UT 84132, USA.

Ming-Hsi Wang (MH)

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.

Jacob L McCauley (JL)

John P. Hussman Institute for Human Genomics, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136 USA; The Dr. John T. Macdonald Foundation Department of Human Genetics, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, USA.

Maria T Abreu (MT)

Division of Gastroenterology, Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, USA; Department of Microbiology and Immunology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, USA.

Traci Jester (T)

Department of Pediatrics, UAB Medicine, Birmingham, AL 35233, USA.

Zarela Molle-Rios (Z)

Pediatric Gastroenterology and Nutrition, Nemours duPont Hospital for Children, DE 19803, USA.

Sirish Palle (S)

Department of Pediatrics, Oklahoma University School of Medicine, Oklahoma City, OK 73104, USA.

Ellen J Scherl (EJ)

Gastroenterology and Hepatology, Jill Roberts Center for IBD, Weill Cornell Medicine, New York, NY 10065, USA.

John Kwon (J)

UT Southwestern Department of Internal Medicine, Dallas, TX 75390, USA.

John D Rioux (JD)

Department of Medicine, Université de Montréal and the Montreal Heart Institute Research Center, Montreal, QC H1Y3N1, Canada.

Richard H Duerr (RH)

Human Genetics, and Clinical and Translational Science, Pittsburgh, PA 15213, USA.

Mark S Silverberg (MS)

Department of Medicine, Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, University of Toronto, Toronto, ON M5T3L9, Canada.

Michael E Zwick (ME)

Department of Human Genetics, Emory University, Atlanta, GA 30322, USA.

Christine Stevens (C)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02115, USA.

Mark J Daly (MJ)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02115, USA.

Judy H Cho (JH)

Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Greg Gibson (G)

Center for Integrative Genomics, Georgia Institute of Technology, Atlanta, GA 30332, USA.

Dermot P B McGovern (DPB)

F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

Steven R Brant (SR)

The Human Genetics Institute of New Jersey, Rutgers University, New Brunswick and Piscataway, NJ 08854, USA.

Subra Kugathasan (S)

Genetics and Molecular Biology Program, Emory University, Atlanta, GA 30322, USA; Division of Pediatric Gastroenterology, Department of Pediatrics, Emory University School of Medicine & Children's Healthcare of Atlanta, Atlanta, GA 30322, USA. Electronic address: skugath@emory.edu.

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Classifications MeSH

questionsmedicales.fr › Personnes › Nord-Américains › Groupes de population aux États-Unis › Populations d'origine continentale › Noir ou Africain Américain › Whole-genome sequencing of African Americans...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Whole-genome sequencing of African Americans...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Sujet âgé de 80 ans ou plus › Whole-genome sequencing of African Americans...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de transport › Protéines de liaison au calcium › Calbindines › Calbindine-2 › Whole-genome sequencing of African Americans...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Maladies inflammatoires intestinales › Rectocolite hémorragique › Whole-genome sequencing of African Americans...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Maladies inflammatoires intestinales › Maladie de Crohn › Whole-genome sequencing of African Americans...
questionsmedicales.fr › Phénomènes génétiques › Fréquence d'allèle › Whole-genome sequencing of African Americans...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Whole-genome sequencing of African Americans...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Whole-genome sequencing of African Americans...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Whole-genome sequencing of African Americans...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Maladies inflammatoires intestinales › Whole-genome sequencing of African Americans...
questionsmedicales.fr › Phénomènes génétiques › Modes de transmission héréditaire › Hérédité multifactorielle › Whole-genome sequencing of African Americans...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Whole-genome sequencing of African Americans...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs couplés aux protéines G › Récepteurs aux éicosanoïdes › Récepteur prostaglandine › Récepteur prostaglandine E › Sous-type EP4 des récepteurs des prostaglandines E › Whole-genome sequencing of African Americans...
questionsmedicales.fr › Personnes › Blancs › Whole-genome sequencing of African Americans...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ADN › Séquençage du génome entier › Whole-genome sequencing of African Americans...