Background Lymphatic filariasis (LF) is a parasitic disease caused by filarial nematodes. An estimated 40 million individuals infected with the filarial nematodes present with the symptomatic LF manifestations of lymphedema (LE) and hydrocele. These symptoms develop in only a subgroup of infected people, and host genetics have been attributed to the disease heterogeneity. Studies that have sought associations between LF and host genetics have focused mainly on candidate genes. The current study aimed to conduct the first genome-wide association study (GWAS) to determine LF susceptibility.

Methods Single nucleotide polymorphism (SNP) data from 3189 participants comprising 1508 LF cases and 1681 asymptomatic controls were analysed in the study. Cases were selected based on the presence of either LE and/or hydrocele while controls consisted of participants who had lived in the endemic community for at least 10 years and had no LE and/or hydrocele. These unrelated participants were genotyped using the Infinium Global screening array with multi-disease drop by Illumina®.

Results Independent signals, rs2245413 and rs2245710 were observed at genome-wide significance (p<5x10–8) to be associated with LF. At the HLA locus, SNP rs7742085 located near the HLA-DQB2 gene was identified at genome-wide significance to be associated with LF susceptibility (P = 3.93 x 10–8, odds ratio [OR] = 1.43 [confidence interval {CI} 1.26–1.63]. Other studies have associated these SNPs with renal abnormalities, LE and hydrocele. Additionally, at three non-HLA loci, close to the genes OR5V1 (rs1419637), RNU6ATAC11P (rs2243492), and PAK1 (rs2852388), suggestive evidence of LF associations (P 1.0 x 10–6) were also observed.

Conclusion This first stage GWAS in Ghanaian population identified novel SNPs associated with LF risk, highlighting the potential of GWAS to provide gene candidates for functional analyses as therapeutic targets toward the World Health Organization’s 2030 elimination goal.