Genome-wide Association Study Identifies HLA-DPB1 as a Significant Risk Factor for Severe Aplastic Anemia.


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:
06 02 2020
Historique:
received: 23 03 2019
accepted: 07 01 2020
pubmed: 1 2 2020
medline: 18 4 2020
entrez: 1 2 2020
Statut: ppublish

Résumé

Severe aplastic anemia (SAA) is a rare disorder characterized by hypoplastic bone marrow and progressive pancytopenia. The etiology of acquired SAA is not understood but is likely related to abnormal immune responses and environmental exposures. We conducted a genome-wide association study of individuals with SAA genetically matched to healthy controls in discovery (359 cases, 1,396 controls) and validation sets (175 cases, 1,059 controls). Combined analyses identified linked SNPs in distinct blocks within the major histocompatibility complex on 6p21. The top SNP encodes p.Met76Val in the P4 binding pocket of the HLA class II gene HLA-DPB1 (rs1042151A>G, odds ratio [OR] 1.75, 95% confidence interval [CI] 1.50-2.03, p = 1.94 × 10

Identifiants

pubmed: 32004448
pii: S0002-9297(20)30004-5
doi: 10.1016/j.ajhg.2020.01.004
pmc: PMC7010969
pii:
doi:

Substances chimiques

Genetic Markers 0
HLA-DP beta-Chains 0
HLA-DPB1 antigen 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

264-271

Subventions

Organisme : NHLBI NIH HHS
ID : U10 HL069294
Pays : United States
Organisme : NCI NIH HHS
ID : N01 PC067009
Pays : United States
Organisme : NCI NIH HHS
ID : N01 PC067010
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA165923
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA076518
Pays : United States
Organisme : NCI NIH HHS
ID : N01 PC067008
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA062006
Pays : United States
Organisme : NCI NIH HHS
ID : N01 PC065064
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA092153
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA097274
Pays : United States
Organisme : CCR NIH HHS
ID : HHSN261200800001C
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States

Informations de copyright

Published by Elsevier Inc.

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Auteurs

Sharon A Savage (SA)

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. Electronic address: savagesh@mail.nih.gov.

Mathias Viard (M)

Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.

Colm O'hUigin (C)

Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA; Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.

Weiyin Zhou (W)

Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA; Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.

Meredith Yeager (M)

Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA; Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.

Shengchao Alfred Li (SA)

Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA; Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.

Tao Wang (T)

Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

Veron Ramsuran (V)

KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.

Nicolas Vince (N)

Université de Nantes, CHU Nantes, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, F-44000 Nantes, France.

Aurelie Vogt (A)

Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA; Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.

Belynda Hicks (B)

Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA; Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.

Laurie Burdett (L)

Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA; Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.

Charles Chung (C)

Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA; Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.

Michael Dean (M)

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.

Kelvin C de Andrade (KC)

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.

Neal D Freedman (ND)

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.

Sonja I Berndt (SI)

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.

Nathaniel Rothman (N)

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.

Qing Lan (Q)

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.

James R Cerhan (JR)

Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55902, USA.

Susan L Slager (SL)

Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55902, USA.

Yawei Zhang (Y)

Section of Surgical Outcomes and Epidemiology, Department of Surgery, Yale Medical School, New Haven, CT 06520, USA.

Lauren R Teras (LR)

Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, 30303, USA.

Michael Haagenson (M)

Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

Stephen J Chanock (SJ)

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.

Stephen R Spellman (SR)

Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

Youjin Wang (Y)

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.

Amanda Willis (A)

Department of Pathology and Laboratory Medicine, Baylor University Medical Center, Dallas, TX 76798, USA.

Medhat Askar (M)

Department of Pathology and Laboratory Medicine, Baylor University Medical Center, Dallas, TX 76798, USA.

Stephanie J Lee (SJ)

Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Mary Carrington (M)

Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA.

Shahinaz M Gadalla (SM)

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.

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Classifications MeSH