First genome-wide association study for lymphatic filariasis in a West African population points to a human leukocyte antigen-mediated disease pathophysiology.
Int J Infect Dis
; 133: 1-4, 2023 Aug.
Article
em En
| MEDLINE
| ID: mdl-37146673
ABSTRACT
OBJECTIVES:
Lymphatic filariasis (LF) represents a parasitic disease caused by filarial nematodes. Although some infected individuals present an asymptomatic course, others suffer severe chronic lymphatic pathology, including lymphedema, hydrocele, and elephantiasis. Several studies have shown that host genetic factors influence LF susceptibility and chronic pathology. The current study aimed to conduct the first genome-wide association study to systematically determine LF susceptibility.METHODS:
We analyzed genome-wide single-nucleotide polymorphism data from 1459 LF cases and 1492 asymptomatic controls of West African (Ghanaian) descent.RESULTS:
We identified two independent genome-wide significant associated genetic variants near the genes HLA-DQB2 (rs7742085) and HLA-DQA1 (rs4959107) contributing to LF and/or lymphedema susceptibility (P <5.0â¯×â¯10-8, odds ratios [ORs] >1.30). We also observed suggestive evidence of LF associations (P <1.0â¯×â¯10-6) at two non-HLA loci, near the genes ZFHX4-AS1 (rs79562145) and CHP2 (rs12933387). In contrast, we could not replicate any previously reported LF associations drawn from candidate gene association studies. On the polygenic level, we show that our genome-wide association study data explain 24-42% of LF heritability, depending on an assumed population prevalence of 0.5-5.0%.CONCLUSION:
Our findings point to an involvement of HLA-mediated immune mechanisms in LF pathophysiology.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Filariose Linfática
/
Linfedema
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
/
Male
País/Região como assunto:
Africa
Idioma:
En
Revista:
Int J Infect Dis
Assunto da revista:
DOENCAS TRANSMISSIVEIS
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Alemanha