PMID- 32488134
OWN - NLM
STAT- MEDLINE
DCOM- 20201217
LR  - 20240501
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 10
IP  - 1
DP  - 2020 Jun 2
TI  - The Human Leukocyte Antigen Locus and Rheumatic Heart Disease Susceptibility in 
      South Asians and Europeans.
PG  - 9004
LID - 10.1038/s41598-020-65855-8 [doi]
LID - 9004
AB  - Rheumatic heart disease (RHD), an autoinflammatory heart disease, was recently 
      declared a global health priority by the World Health Organization. Here we 
      report a genome-wide association study (GWAS) of RHD susceptibility in 1,163 
      South Asians (672 cases; 491 controls) recruited in India and Fiji. We analysed 
      directly obtained and imputed genotypes, and followed-up associated loci in 1,459 
      Europeans (150 cases; 1,309 controls) from the UK Biobank study. We identify a 
      novel susceptibility signal in the class III region of the human leukocyte 
      antigen (HLA) complex in the South Asian dataset that clearly replicates in the 
      Europeans (rs201026476; combined odds ratio 1.81, 95% confidence intervals 
      1.51-2.18, P = 3.48x10(-10)). Importantly, this signal remains despite 
      conditioning on the lead class I and class II variants (P = 0.00033). These 
      findings suggest the class III region is a key determinant of RHD susceptibility 
      offering important new insight into pathogenesis while partly explaining the 
      inconsistency of earlier reports.
FAU - Auckland, Kathryn
AU  - Auckland K
AUID- ORCID: 0000-0002-7583-2886
AD  - The Wellcome Centre for Human Genetics, University of Oxford, Oxford, 
      Oxfordshire, OX3 7BN, UK.
FAU - Mittal, Balraj
AU  - Mittal B
AD  - Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow, 
      226025, Uttar Pradesh, India.
FAU - Cairns, Benjamin J
AU  - Cairns BJ
AD  - MRC Population Health Research Unit, Clinical Trial Service Unit and 
      Epidemiological Studies Unit, Nuffield Department of Population Health, 
      University of Oxford, Oxford, Oxfordshire, OX3 7LF, UK.
FAU - Garg, Naveen
AU  - Garg N
AD  - Department of Cardiology, Sanjay Gandhi Postgraduate Institute of Medical 
      Sciences, Lucknow, 226014, Uttar Pradesh, India.
FAU - Kumar, Surendra
AU  - Kumar S
AD  - Department of Cytogenetics/Anatomy, All India Institute of Medical Sciences, New 
      Delhi, 110029, Delhi, India.
FAU - Mentzer, Alexander J
AU  - Mentzer AJ
AUID- ORCID: 0000-0002-4502-2209
AD  - The Wellcome Centre for Human Genetics, University of Oxford, Oxford, 
      Oxfordshire, OX3 7BN, UK.
FAU - Kado, Joseph
AU  - Kado J
AUID- ORCID: 0000-0003-3121-4397
AD  - Department of Medical Science, Fiji National University, Suva, PO Box 7222, Viti 
      Levu, Fiji.
FAU - Perman, Mai Ling
AU  - Perman ML
AUID- ORCID: 0000-0002-3511-3297
AD  - Department of Medical Science, Fiji National University, Suva, PO Box 7222, Viti 
      Levu, Fiji.
FAU - Steer, Andrew C
AU  - Steer AC
AD  - Tropical Infectious Diseases, Murdoch Children's Research Institute, Melbourne, 
      Victoria, 3052, Australia.
FAU - Hill, Adrian V S
AU  - Hill AVS
AUID- ORCID: 0000-0003-0900-9629
AD  - The Wellcome Centre for Human Genetics, University of Oxford, Oxford, 
      Oxfordshire, OX3 7BN, UK.
FAU - Parks, Tom
AU  - Parks T
AUID- ORCID: 0000-0002-1163-8654
AD  - The Wellcome Centre for Human Genetics, University of Oxford, Oxford, 
      Oxfordshire, OX3 7BN, UK. tom.parks@well.ox.ac.uk.
AD  - Department of Clinical Research, London School of Hygiene & Tropical Medicine, 
      London, Greater London, WC1E 7HT, UK. tom.parks@well.ox.ac.uk.
LA  - eng
GR  - MC_PC_17228/MRC_/Medical Research Council/United Kingdom
GR  - G1100449/MRC_/Medical Research Council/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
GR  - MC_QA137853/MRC_/Medical Research Council/United Kingdom
GR  - PG/14/26/30509/BHF_/British Heart Foundation/United Kingdom
GR  - RE/13/1/30181/BHF_/British Heart Foundation/United Kingdom
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20200602
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Asian People/genetics
MH  - Case-Control Studies
MH  - Fiji
MH  - Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - HLA Antigens/*genetics
MH  - Humans
MH  - India
MH  - Polymorphism, Single Nucleotide
MH  - Rheumatic Heart Disease/*genetics
MH  - White People/genetics
PMC - PMC7265443
COIS- The authors declare no competing interests.
EDAT- 2020/06/04 06:00
MHDA- 2020/12/18 06:00
PMCR- 2020/06/02
CRDT- 2020/06/04 06:00
PHST- 2019/11/04 00:00 [received]
PHST- 2020/05/07 00:00 [accepted]
PHST- 2020/06/04 06:00 [entrez]
PHST- 2020/06/04 06:00 [pubmed]
PHST- 2020/12/18 06:00 [medline]
PHST- 2020/06/02 00:00 [pmc-release]
AID - 10.1038/s41598-020-65855-8 [pii]
AID - 65855 [pii]
AID - 10.1038/s41598-020-65855-8 [doi]
PST - epublish
SO  - Sci Rep. 2020 Jun 2;10(1):9004. doi: 10.1038/s41598-020-65855-8.