PMID- 31519994
OWN - NLM
STAT- MEDLINE
DCOM- 20200316
LR  - 20201216
IS  - 1759-5010 (Electronic)
IS  - 1759-5002 (Linking)
VI  - 17
IP  - 3
DP  - 2020 Mar
TI  - Genetics of rheumatic fever and rheumatic heart disease.
PG  - 145-154
LID - 10.1038/s41569-019-0258-2 [doi]
AB  - Rheumatic heart disease (RHD) is a complication of group A streptococcal 
      infection that results from a complex interaction between the genetic make-up of 
      the host, the infection itself and several other environmental factors, largely 
      reflecting poverty. RHD is estimated to affect 33.4 million people and results in 
      10.5 million disability-adjusted life-years lost globally. The disease has long 
      been considered heritable but still little is known about the host genetic 
      factors that increase or reduce the risk of developing RHD. In the 1980s and 
      1990s, several reports linked the disease to the human leukocyte antigen (HLA) 
      locus on chromosome 6, followed in the 2000s by reports implicating additional 
      candidate regions elsewhere in the genome. Subsequently, the search for 
      susceptibility loci has been reinvigorated by the use of genome-wide association 
      studies (GWAS) through which millions of variants can be tested for association 
      in thousands of individuals. Early findings implicate not only HLA, particularly 
      the HLA-DQA1 to HLA-DQB1 region, but also the immunoglobulin heavy chain locus, 
      including the IGHV4-61 gene segment, on chromosome 14. In this Review, we assess 
      the emerging role of GWAS in assessing RHD, outlining both the advantages and 
      disadvantages of this approach. We also highlight the potential use of 
      large-scale, publicly available data and the value of international collaboration 
      to facilitate comprehensive studies that produce findings that have implications 
      for clinical practice.
FAU - Muhamed, Babu
AU  - Muhamed B
AUID- ORCID: 0000-0003-4832-0671
AD  - Hatter Institute for Cardiovascular Diseases Research in Africa, Department of 
      Medicine, University of Cape Town, Cape Town, South Africa.
FAU - Parks, Tom
AU  - Parks T
AUID- ORCID: 0000-0002-1163-8654
AD  - Faculty of Infectious and Tropical Diseases, London School of Hygiene and 
      Tropical Medicine, London, UK.
AD  - Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
FAU - Sliwa, Karen
AU  - Sliwa K
AD  - Hatter Institute for Cardiovascular Diseases Research in Africa, Department of 
      Medicine, University of Cape Town, Cape Town, South Africa. 
      karen.sliwa-hahnle@uct.ac.za.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20190913
PL  - England
TA  - Nat Rev Cardiol
JT  - Nature reviews. Cardiology
JID - 101500075
RN  - 0 (HLA-DQ alpha-Chains)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQA1 antigen)
RN  - 0 (HLA-DQB1 antigen)
SB  - IM
MH  - Animals
MH  - Genes, Immunoglobulin Heavy Chain
MH  - *Genetic Loci
MH  - Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - HLA-DQ alpha-Chains/genetics/immunology
MH  - HLA-DQ beta-Chains/genetics/immunology
MH  - Humans
MH  - Phenotype
MH  - Rheumatic Fever/epidemiology/*genetics/immunology
MH  - Rheumatic Heart Disease/epidemiology/*genetics/immunology
MH  - Risk Assessment
MH  - Risk Factors
EDAT- 2019/09/15 06:00
MHDA- 2020/03/17 06:00
CRDT- 2019/09/15 06:00
PHST- 2019/08/09 00:00 [accepted]
PHST- 2019/09/15 06:00 [pubmed]
PHST- 2020/03/17 06:00 [medline]
PHST- 2019/09/15 06:00 [entrez]
AID - 10.1038/s41569-019-0258-2 [pii]
AID - 10.1038/s41569-019-0258-2 [doi]
PST - ppublish
SO  - Nat Rev Cardiol. 2020 Mar;17(3):145-154. doi: 10.1038/s41569-019-0258-2. Epub 
      2019 Sep 13.