Association of Novel Locus With Rheumatic Heart Disease in Black African Individuals

Autor: Babu Muhamed, Agnes Mtaja, Tom Parks, Shahiemah Pandie, Huda H.M. Elhassan, Mark E Engel, Goeffrey Madeira, Emmy Okello, Michael Chong, Ahmed Elsayed, Guillaume Paré, Bernard Keavney, Tafadzwa Machipisa, Ana Olga Mocumbi, Nakita Laing, Nicola Mulder, John Musuku, Liesl Zühlke, Célia Novela, Maia Lesosky, Jantina de Vries, Alexia Joachim, Gasnat Shaboodien, Chishala Chishala, Raj Ramesar, Fidelia Bode-Thomas, Bernard Gitura, Albertino Damasceno, Stephen Ogendo, Mpiko Ntsekhe, Basil N Okeahialam, Peter Lwabi, Rezeen Daniels, Christopher Hugo-Hamman, Heather J. Cordell
Rok vydání: 2021
Předmět:
Male
Proband
Multifactorial Inheritance
Cardiac & Cardiovascular Systems
Health Status
Genome-wide association study
030204 cardiovascular system & hematology
Cardiovascular System
MIXED-MODEL
0302 clinical medicine
GWAS
030212 general & internal medicine
Child
Original Investigation
RISK
Incidence
Blacks
Middle Aged
Echocardiography
Disease Progression
Pacific islanders
Rheumatic fever
Female
Cardiology and Cardiovascular Medicine
Life Sciences & Biomedicine
Adult
GENETICS
Adolescent
Genotype
Black People
Locus (genetics)
Polymorphism
Single Nucleotide
Young Adult
03 medical and health sciences
FEVER
Genetic predisposition
medicine
Humans
Genetic Predisposition to Disease
INCOME COUNTRIES
GENOME-WIDE ASSOCIATION
COMMON
Retrospective Studies
Science & Technology
business.industry
Rheumatic Heart Disease
Odds ratio
Heritability
medicine.disease
REGISTRY
Africa
Cardiovascular System & Cardiology
business
Follow-Up Studies
Genome-Wide Association Study
Demography
Zdroj: JAMA Cardiol
ISSN: 2380-6583
DOI: 10.1001/jamacardio.2021.1627
Popis: IMPORTANCE: Rheumatic heart disease (RHD), a sequela of rheumatic fever characterized by permanent heart valve damage, is the leading cause of cardiac surgery in Africa. However, its pathophysiologic characteristics and genetics are poorly understood. Understanding genetic susceptibility may aid in prevention, control, and interventions to eliminate RHD. OBJECTIVE: To identify common genetic loci associated with RHD susceptibility in Black African individuals. DESIGN, SETTING, AND PARTICIPANTS: This multicenter case-control genome-wide association study (GWAS), the Genetics of Rheumatic Heart Disease, examined more than 7 million genotyped and imputed single-nucleotide variations. The 4809 GWAS participants and 116 independent trio families were enrolled from 8 African countries between December 31, 2012, and March 31, 2018. All GWAS participants and trio probands were screened by use of echocardiography. Data analyses took place from May 15, 2017, until March 14, 2021. MAIN OUTCOMES AND MEASURES: Genetic associations with RHD. RESULTS: This study included 4809 African participants (2548 RHD cases and 2261 controls; 3301 women [69%]; mean [SD] age, 36.5 [16.3] years). The GWAS identified a single RHD risk locus, 11q24.1 (rs1219406 [odds ratio, 1.65; 95% CI, 1.48-1.82; P = 4.36 × 10(−8)]), which reached genome-wide significance in Black African individuals. Our meta-analysis of Black (n = 3179) and admixed (n = 1055) African individuals revealed several suggestive loci. The study also replicated a previously reported association in Pacific Islander individuals (rs11846409) at the immunoglobulin heavy chain locus, in the meta-analysis of Black and admixed African individuals (odds ratio, 1.16; 95% CI, 1.06-1.27; P = 1.19 × 10(−3)). The HLA (rs9272622) associations reported in Aboriginal Australian individuals could not be replicated. In support of the known polygenic architecture for RHD, overtransmission of a polygenic risk score from unaffected parents to affected probands was observed (polygenic transmission disequilibrium testing mean [SE], 0.27 [0.16] SDs; P = .04996), and the chip-based heritability was estimated to be high at 0.49 (SE = 0.12; P = 3.28 × 10(−5)) in Black African individuals. CONCLUSIONS AND RELEVANCE: This study revealed a novel candidate susceptibility locus exclusive to Black African individuals and an important heritable component to RHD susceptibility in African individuals.
Databáze: OpenAIRE
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