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Multiethnic Genome-Wide Association Study of Diabetic Retinopathy Using Liability Threshold Modeling of Duration of Diabetes and Glycemic Control

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

Diabetes (New York, N.Y.), 2019-02, Vol.68 (2), p.441-456 [Periódico revisado por pares]

United States: American Diabetes Association

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Título:
Multiethnic Genome-Wide Association Study of Diabetic Retinopathy Using Liability Threshold Modeling of Duration of Diabetes and Glycemic Control
Autor: Pollack, Samuela ; Igo, Jr, Robert P ; Jensen, Richard A ; Christiansen, Mark ; Li, Xiaohui ; Cheng, Ching-Yu ; Ng, Maggie C Y ; Smith, Albert V ; Rossin, Elizabeth J ; Segrè, Ayellet V ; Davoudi, Samaneh ; Tan, Gavin S ; Chen, Yii-Der Ida ; Kuo, Jane Z ; Dimitrov, Latchezar M ; Stanwyck, Lynn K ; Meng, Weihua ; Hosseini, S Mohsen ; Imamura, Minako ; Nousome, Darryl ; Kim, Jihye ; Hai, Yang ; Jia, Yucheng ; Ahn, Jeeyun ; Leong, Aaron ; Shah, Kaanan ; Park, Kyu Hyung ; Guo, Xiuqing ; Ipp, Eli ; Taylor, Kent D ; Adler, Sharon G ; Sedor, John R ; Freedman, Barry I ; Lee, I-Te ; Sheu, Wayne H-H ; Kubo, Michiaki ; Takahashi, Atsushi ; Hadjadj, Samy ; Marre, Michel ; Tregouet, David-Alexandre ; Mckean-Cowdin, Roberta ; Varma, Rohit ; McCarthy, Mark I ; Groop, Leif ; Ahlqvist, Emma ; Lyssenko, Valeriya ; Agardh, Elisabet ; Morris, Andrew ; Doney, Alex S F ; Colhoun, Helen M ; Toppila, Iiro ; Sandholm, Niina ; Groop, Per-Henrik ; Maeda, Shiro ; Hanis, Craig L ; Penman, Alan ; Chen, Ching J ; Hancock, Heather ; Mitchell, Paul ; Craig, Jamie E ; Chew, Emily Y ; Paterson, Andrew D ; Grassi, Michael A ; Palmer, Colin ; Bowden, Donald W ; Yaspan, Brian L ; Siscovick, David ; Cotch, Mary Frances ; Wang, Jie Jin ; Burdon, Kathryn P ; Wong, Tien Y ; Klein, Barbara E K ; Klein, Ronald ; Rotter, Jerome I ; Iyengar, Sudha K ; Price, Alkes L ; Sobrin, Lucia
Assuntos: Basic Medicine ; Blood Glucose - metabolism ; Clinical Medicine ; Complications ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus, Type 2 - genetics ; Diabetes Mellitus, Type 2 - metabolism ; Diabetic Retinopathy ; Endocrinology and Diabetes ; Endokrinologi och diabetes ; Genetic analysis ; Genetic diversity ; Genetic Predisposition to Disease ; Genome-wide association studies ; Genome-Wide Association Study - methods ; Genomes ; Genotype ; Glucose monitoring ; Glycated Hemoglobin - metabolism ; Humans ; Klinisk medicin ; Medical and Health Sciences ; Medical Genetics ; Medicin och hälsovetenskap ; Medicinsk genetik ; Medicinska och farmaceutiska grundvetenskaper ; Meta-Analysis as Topic ; Polymorphism, Single Nucleotide - genetics ; Protein Binding ; Proteins ; Replication ; Retinopathy
É parte de: Diabetes (New York, N.Y.), 2019-02, Vol.68 (2), p.441-456
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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A.L.P. and L.S. contributed equally to this work.
Descrição: 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.
Editor: United States: American Diabetes Association
Idioma: Inglês

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Multiethnic Genome-Wide Association Study of Diabetic Retinopathy Using Liability Threshold Modeling of Duration of Diabetes and Glycemic Control

United States: American Diabetes Association

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