| Title: |
Multiethnic genome-wide association study of diabetic retinopathy using liability threshold modeling of duration of diabetes and glycemic control |
| Authors: |
Pollack, S; Igo Jr, RP; Jensen, RA; Christiansen, M; Li, X; Cheng, CY; Ng, MCY; Smith, AV; Rossin, EJ; Segre, AV; Davoudi, S; Tan, GS; Chen, Y-DI; Kuo, JZ; Dimitrov, LM; Stanwyck, LK; Meng, W; Hosseini, SM; Imamura, M; Nousome, D; Kim, J; Hai, Y; Jia, Y; Ahn, J; Leong, A; Shah, K; Park, KH; Guo, X; Ipp, E; Taylor, KD; Adler, SG; Sedor, JR; Freedman, BI; Lee, I-T; Sheu, WH-H; Kubo, M; Takahashi, A; Hadjadj, S; Marre, M; Tregouet, D-A; Mckean-Cowdin, R; Varma, R; McCarthy, MI; Groop, L; Ahlqvist, E; Lyssenko, V; Agardh, E; Morris, A; Doney, ASF; Colhoun, HM; Toppila, I; Sandholm, N; Groop, P-H; Maeda, S; Hanis, CL; Penman, A; Chen, CJ; Hancock, H; Mitchell, P; Craig, JE; Chew, EY; Paterson, AD; Grassi, MA; Palmer, C; Bowden, DW; Yaspan, BL; Siscovick, D; Cotch, MF; Wang, JJ; Kathryn Burdon; Wong, TY; Klein, BEK; Klein, R; Rotter, JI; Iyengar, SK; Price, AL; Sobrin, L |
| Publication Year: |
2018 |
| Subject Terms: |
Ophthalmology; genome; diabetic retinopathy; diabetes; glycemic control |
| Description: |
To identify genetic variants associated with diabetic retinopathy (DR), we performed a large, multiethnic genome-wide association study (GWAS). Discovery included eight European cohorts ( n = 3,246) and seven African American cohorts ( n = 2,611). We meta-analyzed across cohorts using inverse-variance weighting, with and without liability threshold modeling of glycemic control and duration of diabetes. Variants with a P value < 1 X 10 -5 were investigated in replication cohorts that included 18,545 Europeans, 16,453 Asians and 2,710 Hispanics. After correction for multiple testing, the C allele of rs142293996 in an intron of nuclear VCP-like ( NVL ) was associated with DR in European discovery cohorts ( P = 2.1 x 10 -9 ), but did not reach genome-wide significance after meta-analysis with replication cohorts. We applied the Disease Association Protein-Protein Link Evaluator (DAPPLE) to our discovery results to test for evidence of risk being spread across underlying molecular pathways. One protein-protein interaction network built from genes in regions associated with proliferative DR (PDR) was found to have significant connectivity ( P =0.0009) and corroborated with gene set enrichment analyses. These findings suggest that genetic variation in NVL , as well as variation within a protein-protein interaction network that includes genes implicated in inflammation, may influence risk for DR. |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| Relation: |
102.100.100/560656 |
| Availability: |
https://figshare.com/articles/journal_contribution/Multiethnic_genome-wide_association_study_of_diabetic_retinopathy_using_liability_threshold_modeling_of_duration_of_diabetes_and_glycemic_control/22974479 |
| Rights: |
In Copyright |
| Accession Number: |
edsbas.FB85967 |
| Database: |
BASE |