TY - JOUR T1 - Multiethnic Genome-Wide Association Study of Diabetic Retinopathy Using Liability Threshold Modeling of Duration of Diabetes and Glycemic Control. JF - Diabetes Y1 - 2019 A1 - Pollack, Samuela A1 - Igo, Robert P A1 - Jensen, Richard A A1 - Christiansen, Mark A1 - Li, Xiaohui A1 - Cheng, Ching-Yu A1 - Ng, Maggie C Y A1 - Smith, Albert V A1 - Rossin, Elizabeth J A1 - Segrè, Ayellet V A1 - Davoudi, Samaneh A1 - Tan, Gavin S A1 - Chen, Yii-Der Ida A1 - Kuo, Jane Z A1 - Dimitrov, Latchezar M A1 - Stanwyck, Lynn K A1 - Meng, Weihua A1 - Hosseini, S Mohsen A1 - Imamura, Minako A1 - Nousome, Darryl A1 - Kim, Jihye A1 - Hai, Yang A1 - Jia, Yucheng A1 - Ahn, Jeeyun A1 - Leong, Aaron A1 - Shah, Kaanan A1 - Park, Kyu Hyung A1 - Guo, Xiuqing A1 - Ipp, Eli A1 - Taylor, Kent D A1 - Adler, Sharon G A1 - Sedor, John R A1 - Freedman, Barry I A1 - Lee, I-Te A1 - Sheu, Wayne H-H A1 - Kubo, Michiaki A1 - Takahashi, Atsushi A1 - Hadjadj, Samy A1 - Marre, Michel A1 - Trégouët, David-Alexandre A1 - McKean-Cowdin, Roberta A1 - Varma, Rohit A1 - McCarthy, Mark I A1 - Groop, Leif A1 - Ahlqvist, Emma A1 - Lyssenko, Valeriya A1 - Agardh, Elisabet A1 - Morris, Andrew A1 - Doney, Alex S F A1 - Colhoun, Helen M A1 - Toppila, Iiro A1 - Sandholm, Niina A1 - Groop, Per-Henrik A1 - Maeda, Shiro A1 - Hanis, Craig L A1 - Penman, Alan A1 - Chen, Ching J A1 - Hancock, Heather A1 - Mitchell, Paul A1 - Craig, Jamie E A1 - Chew, Emily Y A1 - Paterson, Andrew D A1 - Grassi, Michael A A1 - Palmer, Colin A1 - Bowden, Donald W A1 - Yaspan, Brian L A1 - Siscovick, David A1 - Cotch, Mary Frances A1 - Wang, Jie Jin A1 - Burdon, Kathryn P A1 - Wong, Tien Y A1 - Klein, Barbara E K A1 - Klein, Ronald A1 - Rotter, Jerome I A1 - Iyengar, Sudha K A1 - Price, Alkes L A1 - Sobrin, Lucia AB -

To identify genetic variants associated with diabetic retinopathy (DR), we performed a large multiethnic genome-wide association study. Discovery included eight European cohorts ( = 3,246) and seven African American cohorts ( = 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 value <1 × 10 were investigated in replication cohorts that included 18,545 European, 16,453 Asian, and 2,710 Hispanic subjects. After correction for multiple testing, the C allele of rs142293996 in an intron of nuclear VCP-like () was associated with DR in European discovery cohorts ( = 2.1 × 10), 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 was found to have significant connectivity ( = 0.0009) and corroborated with gene set enrichment analyses. These findings suggest that genetic variation in as well as variation within a protein-protein interaction network that includes genes implicated in inflammation, may influence risk for DR.

VL - 68 IS - 2 ER -