Genetic Association at the 9p21 Glaucoma Locus Contributes to Sex Bias in Normal-Tension Glaucoma

Abstract

This study demonstrated that female sex is a risk factor for developing advanced NTG. The stronger genetic signals at the 9p21 locus among females may contribute at least in part to the observed sex bias for NTG.

Author Response: Stronger Association of CDKN2B-AS1 Variants in Female Normal-Tension Glaucoma Patients in a Japanese Population

“…As pointed out in our original publication, 2 the robust replication of genetic findings in independent populations is vital in understanding the significance of any reported association. Mori et al 1 have provided strong additional evidence for a sex-biased association with primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG) at this locus.…”

Stronger Association of CDKN2B-AS1 Variants in Female Normal-Tension Glaucoma Patients in a Japanese Population

“…We read with great interest the article by Ng et al 1 entitled ''Genetic Association at the 9p21 Glaucoma Locus Contributes to Sex Bias in Normal-Tension Glaucoma,'' that was recently published in Investigative Ophthalmology & Visual Science. As the 9p21 locus was identified by a genome-wide association study (GWAS) to be associated with primary open-angle glaucoma (POAG), and the association was found to be significantly stronger among the normal-tension glaucoma (NTG) subgroup (for review see Ref.…”

“…2), Ng et al 1 extended the analysis to investigate the influence of sex difference on the genetic association at the 9p21 locus. They carefully analyzed the genotype data of 13 variants linked with clinical information and clearly presented the results that: (1) the sex bias was present within advanced NTG cases, (2) the strongest associated variant in all POAG cases showed stronger association in females than in males with a statistically significant difference in female-to-male odds ratio (OR) comparison, and (3) the significant association was observed only in females under the NTG to high-tension glaucoma (HTG) subanalysis along with a significant difference in OR comparison.…”

“…We ended up with 975 healthy controls and 1244 POAG cases composed of 545 HTG and 699 NTG patients (HTG and NTG were denoted as HPG and NPG, respectively, in our previous article 4 ) for the analysis (Table 1). Among the 13 variants at the 9p21 locus that Ng et al 1 analyzed, we were able to directly compare the genotype data of three variants on CDKN2B-AS1 from our previous datasets. With regard to the female-to-male analyses, we indeed observed a stronger association for all of the variants in the female patients (Table 2).…”

“…Not only identifying the genetic variants responsible for the disease onset by casecontrol association studies, but also carefully linking these phenotypes to each identified variant (as Ng et al 1 performed for the sex difference), should greatly contribute to the elucidation of the complex etiology of glaucoma. …”