03502nas a2200793 4500008004100000022001400041245011400055210006900169260001200238300001400250490000700264520132200271653000901593653002501602653001101627653003401638653001101672653001101683653000901694653003701703653001601740653003601756653000901792100001801801700002001819700001401839700001601853700002201869700002201891700002001913700001501933700001901948700002001967700001801987700001702005700001702022700001402039700001302053700002102066700002102087700001702108700001702125700001902142700001702161700002102178700002402199700001502223700002402238700001402262700001602276700002602292700002002318700001802338700002302356700001802379700002502397700001902422700001702441700001902458700002202477700002202499700001802521700002002539700002302559700002002582700002002602710005002622856003602672 2017 eng d a1939-327X00aGenetically Determined Plasma Lipid Levels and Risk of Diabetic Retinopathy: A Mendelian Randomization Study.0 aGenetically Determined Plasma Lipid Levels and Risk of Diabetic c2017 12 a3130-31410 v663 a
Results from observational studies examining dyslipidemia as a risk factor for diabetic retinopathy (DR) have been inconsistent. We evaluated the causal relationship between plasma lipids and DR using a Mendelian randomization approach. We pooled genome-wide association studies summary statistics from 18 studies for two DR phenotypes: any DR (N = 2,969 case and 4,096 control subjects) and severe DR (N = 1,277 case and 3,980 control subjects). Previously identified lipid-associated single nucleotide polymorphisms served as instrumental variables. Meta-analysis to combine the Mendelian randomization estimates from different cohorts was conducted. There was no statistically significant change in odds ratios of having any DR or severe DR for any of the lipid fractions in the primary analysis that used single nucleotide polymorphisms that did not have a pleiotropic effect on another lipid fraction. Similarly, there was no significant association in the Caucasian and Chinese subgroup analyses. This study did not show evidence of a causal role of the four lipid fractions on DR. However, the study had limited power to detect odds ratios less than 1.23 per SD in genetically induced increase in plasma lipid levels, thus we cannot exclude that causal relationships with more modest effect sizes exist.
10aAged10aDiabetic Retinopathy10aFemale10aGenome-Wide Association Study10aHumans10aLipids10aMale10aMendelian Randomization Analysis10aMiddle Aged10aPolymorphism, Single Nucleotide10aRisk1 aSobrin, Lucia1 aChong, Yong, He1 aFan, Qiao1 aGan, Alfred1 aStanwyck, Lynn, K1 aKaidonis, Georgia1 aCraig, Jamie, E1 aKim, Jihye1 aLiao, Wen-Ling1 aHuang, Yu-Chuen1 aLee, Wen-Jane1 aHung, Yi-Jen1 aGuo, Xiuqing1 aHai, Yang1 aIpp, Eli1 aPollack, Samuela1 aHancock, Heather1 aPrice, Alkes1 aPenman, Alan1 aMitchell, Paul1 aLiew, Gerald1 aSmith, Albert, V1 aGudnason, Vilmundur1 aTan, Gavin1 aKlein, Barbara, E K1 aKuo, Jane1 aLi, Xiaohui1 aChristiansen, Mark, W1 aPsaty, Bruce, M1 aSandow, Kevin1 aJensen, Richard, A1 aKlein, Ronald1 aCotch, Mary, Frances1 aWang, Jie, Jin1 aJia, Yucheng1 aChen, Ching, J1 aChen, Yii-Der Ida1 aRotter, Jerome, I1 aTsai, Fuu-Jen1 aHanis, Craig, L1 aBurdon, Kathryn, P1 aWong, Tien, Yin1 aCheng, Ching-Yu1 aAsian Genetic Epidemiology Network Consortium uhttps://chs-nhlbi.org/node/759004450nas a2201069 4500008004100000022001400041245015100055210006900206260001300275300001200288490000700300520139200307100002101699700001901720700002301739700002301762700001601785700002001801700001901821700002101840700002501861700002301886700002101909700001801930700002201948700001701970700002701987700002202014700001702036700002102053700002002074700002002094700001502114700001402129700001702143700001602160700001702176700001702193700002102210700001702231700001302248700002002261700002102281700001902302700002302321700001402344700002102358700001902379700002302398700001802421700001802439700003202457700002702489700001702516700002202533700001602555700001902571700002302590700002102613700001902634700002102653700002202674700001802696700002002714700002202734700001702756700002002773700001702793700001902810700002102829700001902850700002002869700001902889700002402908700002302932700001802955700002202973700002102995700002103016700002503037700001903062700002303081700001803104700002403122700001803146700002203164700002203186700002003208700001803228710009803246856003603344 2019 eng d a1939-327X00aMultiethnic Genome-Wide Association Study of Diabetic Retinopathy Using Liability Threshold Modeling of Duration of Diabetes and Glycemic Control.0 aMultiethnic GenomeWide Association Study of Diabetic Retinopathy c2019 Feb a441-4560 v683 aTo 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.
1 aPollack, Samuela1 aIgo, Robert, P1 aJensen, Richard, A1 aChristiansen, Mark1 aLi, Xiaohui1 aCheng, Ching-Yu1 aC Y Ng, Maggie1 aSmith, Albert, V1 aRossin, Elizabeth, J1 aSegrè, Ayellet, V1 aDavoudi, Samaneh1 aTan, Gavin, S1 aChen, Yii-Der Ida1 aKuo, Jane, Z1 aDimitrov, Latchezar, M1 aStanwyck, Lynn, K1 aMeng, Weihua1 aHosseini, Mohsen1 aImamura, Minako1 aNousome, Darryl1 aKim, Jihye1 aHai, Yang1 aJia, Yucheng1 aAhn, Jeeyun1 aLeong, Aaron1 aShah, Kaanan1 aPark, Kyu, Hyung1 aGuo, Xiuqing1 aIpp, Eli1 aTaylor, Kent, D1 aAdler, Sharon, G1 aSedor, John, R1 aFreedman, Barry, I1 aLee, I-Te1 aSheu, Wayne, H-H1 aKubo, Michiaki1 aTakahashi, Atsushi1 aHadjadj, Samy1 aMarre, Michel1 aTrégouët, David-Alexandre1 aMcKean-Cowdin, Roberta1 aVarma, Rohit1 aMcCarthy, Mark, I1 aGroop, Leif1 aAhlqvist, Emma1 aLyssenko, Valeriya1 aAgardh, Elisabet1 aMorris, Andrew1 aDoney, Alex, S F1 aColhoun, Helen, M1 aToppila, Iiro1 aSandholm, Niina1 aGroop, Per-Henrik1 aMaeda, Shiro1 aHanis, Craig, L1 aPenman, Alan1 aChen, Ching, J1 aHancock, Heather1 aMitchell, Paul1 aCraig, Jamie, E1 aChew, Emily, Y1 aPaterson, Andrew, D1 aGrassi, Michael, A1 aPalmer, Colin1 aBowden, Donald, W1 aYaspan, Brian, L1 aSiscovick, David1 aCotch, Mary, Frances1 aWang, Jie, Jin1 aBurdon, Kathryn, P1 aWong, Tien, Y1 aKlein, Barbara, E K1 aKlein, Ronald1 aRotter, Jerome, I1 aIyengar, Sudha, K1 aPrice, Alkes, L1 aSobrin, Lucia1 aFamily Investigation of Nephropathy and Diabetes-Eye Research Group, DCCT/EDIC Research Group uhttps://chs-nhlbi.org/node/7990