A genome-wide association study implicates that the TTC39C gene is associated with diabetic maculopathy with decreased visual acuity

Abstract

21 Background: Diabetic maculopathy is a form of diabetic retinopathy. The visual acuity of one 22 third of patients with diabetic maculopathy will be affected. The purpose of this study was to 23 identify genetic contributors of diabetic maculopathy with decreased visual acuity based on a 24 genome-wide association approach using a well-defined Scottish diabetic cohort. 25 Methods: We used linked e-health records of diabetic patients to define our cases and 26 controls. The cases in this study were defined as type 2 diabetic patients who had ever been 27 recorded in the linked e-health records as having maculopathy (observable or referable) in at 28 least one eye and whose visual acuity of the eye was recorded to have decreased between the 29 first and the last visual acuity record of that eye in the longitudinal e-health records. The 30 controls were defined as a type 2 diabetic individual who had never been diagnosed with 31 maculopathy or retinopathy in the linked e-health records. Anyone who had laser 32 photocoagulation treatment was also excluded from the controls. A standard genome-wide 33 association approach was applied. 34 Results: Overall, we identified 469 cases and 1,374 controls within the Genetics of Diabetes 35 Audit and Research in Tayside Scotland (GoDARTS) dataset. We found that the P value of 36 rs9966620 in the TTC39C gene was 4.13x10-8 , which reached genome-wide significance. 37 Conclusions: We suggest that the TTC39C gene is associated with diabetic maculopathy with 38 decreased visual acuity. This needs to be confirmed by further replication studies and functional 39 studies.

Single-cell multiome of the human retina and deep learning nominate causal variants in complex eye diseases

“…These included rs9966620, the top SNP from a GWAS of DR representing a G-to-A transition in an intron of TTC39C on chromosome 18. 34 Using our multiome, we determined that the scATAC peak containing rs9966620 was most accessible in rods ( Figure 5C ). However, this peak also correlated with the expression of multiple target genes, hampering efforts to interpret how the SNP might function.…”

Single-cell multiome of the human retina and deep learning nominate causal variants in complex eye diseases

“…We found 187 disease-associated SNPs in scATAC peaks that were linked to a gene by a H3K27ac HiChIP loop. These included rs9966620, the top SNP from a GWAS of DR representing a G-to-A transition in an intron of TTC39C on chromosome 18 32 . Using our multiome, we determined that the scATAC peak containing rs9966620 was most accessible in rods (Fig.…”

Ttc39c is a potential target for the treatment of lung cancer

“…The protein encoded by the Ttc39c gene contains several putative tetrapeptide repeat (TPR) domains, which are structural motifs that facilitate protein interaction [18]. Ttc39c strongly influences muscle cell signal transduction and differentiation.…”

“…The expression of the Ttc39c gene is significantly upregulated in STK11 mutant lung cancer tissue samples [17]. The protein encoded by the Ttc39c gene contains several putative tetrapeptide repeat (TPR) domains, which form a structural motif that promotes protein-protein interactions [18]. The TPR domain affects cell cycle regulation and signal domain [19,20].…”