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

Monday,2019-03-18 15:55 America/Los_Angeles — ecterry
TitleMultiethnic Genome-Wide Association Study of Diabetic Retinopathy Using Liability Threshold Modeling of Duration of Diabetes and Glycemic Control.
Publication TypeJournal Article
Year of Publication2019
AuthorsPollack, S, Igo, RP, Jensen, RA, Christiansen, M, Li, X, Cheng, C-Y, C Y Ng, M, Smith, AV, Rossin, EJ, Segrè, AV, Davoudi, S, Tan, GS, Chen, Y-DI, Kuo, JZ, Dimitrov, LM, Stanwyck, LK, Meng, W, S Hosseini, M, Imamura, M, Nousome, D, Kim, J, Hai, Y, Jia, Y, Ahn, J, Leong, A, Shah, K, Park, KHyung, 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, Trégouët, 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, MFrances, Wang, JJin, Burdon, KP, Wong, TY, Klein, BEK, Klein, R, Rotter, JI, Iyengar, SK, Price, AL, Sobrin, L
Corporate/Institutional AuthorsFamily Investigation of Nephropathy and Diabetes-Eye Research Group, DCCT/EDIC Research Group
JournalDiabetes
Volume68
Issue2
Pagination441-456
Date Published2019 Feb
ISSN1939-327X
Abstract<p>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.</p>
DOI10.2337/db18-0567
Alternate JournalDiabetes
PubMed ID30487263
PubMed Central IDPMC6341299
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
RC2 HL102419 / HL / NHLBI NIH HHS / United States
P30 EY001792 / EY / NEI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
HHSN268201500003C / HL / NHLBI NIH HHS / United States
U01 DK057304 / DK / NIDDK NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
R01 DK084149 / DK / NIDDK NIH HHS / United States
R01 DK070941 / DK / NIDDK NIH HHS / United States
U01 HL041654 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
U01 DK057298 / DK / NIDDK NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
U01 DK057295 / DK / NIDDK NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
ZIA EY000403 / EY / NEI NIH HHS / United States
U01 DK105556 / DK / NIDDK NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
U01 DK057300 / DK / NIDDK NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
K12 EY016335 / EY / NEI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
R01 HG006399 / HG / NHGRI NIH HHS / United States
R01 EY012386 / EY / NEI NIH HHS / United States
U01 DK057303 / DK / NIDDK NIH HHS / United States
HHSN268201300048C / HL / NHLBI NIH HHS / United States
R01 EY023644 / EY / NEI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
N01HC95164 / HL / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
U01 HL041652 / HL / NHLBI NIH HHS / United States
N02HL64278 / HL / NHLBI NIH HHS / United States
N01HC95162 / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
N01HC95168 / HL / NHLBI NIH HHS / United States
R01 DK087914 / DK / NIDDK NIH HHS / United States
U01 DK057249 / DK / NIDDK NIH HHS / United States
R01 DK073541 / DK / NIDDK NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268201300049C / HL / NHLBI NIH HHS / United States
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HHSN268201200036C / HL / NHLBI NIH HHS / United States
HHSN268201800001C / HL / NHLBI NIH HHS / United States
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R01 DK047487 / DK / NIDDK NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
N01HC95165 / HL / NHLBI NIH HHS / United States
N01HC95159 / HL / NHLBI NIH HHS / United States
N01HC95161 / HL / NHLBI NIH HHS / United States
HHSN268201300047C / HL / NHLBI NIH HHS / United States
HHSN268201300050C / HL / NHLBI NIH HHS / United States
ZIA AG007380 / AG / NIA NIH HHS / United States
U01 DK057329 / DK / NIDDK NIH HHS / United States
M01 RR007122 / RR / NCRR NIH HHS / United States
M01 RR000425 / RR / NCRR NIH HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
N01HC95167 / HL / NHLBI NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
R01 DK053591 / DK / NIDDK NIH HHS / United States
M01 RR000997 / RR / NCRR NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
/ / Wellcome Trust / United Kingdom
HHSN268201300046C / HL / NHLBI NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States
U01 DK057292 / DK / NIDDK NIH HHS / United States
N01CO12400 / CA / NCI NIH HHS / United States
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N01HC95166 / HL / NHLBI NIH HHS / United States
R01 EY022302 / EY / NEI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
M01 RR000827 / RR / NCRR NIH HHS / United States
M01 RR000080 / RR / NCRR NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States
ZIA EY000401 / EY / NEI NIH HHS / United States
U10 EY011753 / EY / NEI NIH HHS / United States
U01 HL065520 / HL / NHLBI NIH HHS / United States
U01 DK070657 / DK / NIDDK NIH HHS / United States
M01 RR001346 / RR / NCRR NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
ePub date: 
19/02

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