First genome-wide association study for lymphatic filariasis in a West African population points to an HLA-mediated disease pathophysiology.

OBJECTIVES: Lymphatic filariasis (LF) represents a parasitic disease caused by filarial nematodes. While some infected individuals present an asymptomatic course, others suffer severe chronic lymphatic pathology, including lymphoedema (LE), hydrocele, and elephantiasis. Several studies have shown that host genetic factors influence LF susceptibility and chronic pathology. The present study aimed to conduct the first genome-wide association study (GWAS) to systematically determine LF susceptibility.

METHODS: We analyzed genome-wide single-nucleotide polymorphism (SNP) data from 1,459 LF cases and 1,492 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 LE susceptibility (P < 5.0 × 10-8 , odds ratios (ORs) > 1.30). We also observed suggestive evidence of LF associations (P < 1.0 × 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 GWAS 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.