A susceptibility locus rs7099208 is associated with non-obstructive azoospermia via reduction in the expression of FAM160B1

Non-obstructive azoospermia (NOA) is a severe defect in male reproductive health that occurs in 1% of adult men. In a previous study, we identified that rs7099208 is located within the last intron of FAM160B1 at 10q25.3. In this study, we analysed expression Quantitative Trait Loci (eQTL) of FAM160B1, ABLIM1 and TRUB1, the three genes surrounding rs7099208. Only the expression level of FAM160B1 was reduced for the homozygous alternate genotype (GG) of rs7099208, but not for the homozygous reference or heterozygous genotypes. FAM160B1 is predominantly expressed in human testes, where it is found in spermatocytes and round spermatids. From 17 patients with NOA and five with obstructive azoospermia (OA), immunohistochemistry revealed that expression of FAM160B1 is reduced, or undetectable in NOA patients, but not in OA cases or normal men. We conclude that rs7099208 is associated with NOA via a reduction in the expression of FAM160B1.