TY - JOUR
T1 - Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error
T2 - the CREAM consortium
AU - The CREAM Consortium
AU - Li, Qing
AU - Wojciechowski, Robert
AU - Simpson, Claire L.
AU - Hysi, Pirro G.
AU - Verhoeven, Virginie J.M.
AU - Ikram, Mohammad Kamran
AU - Höhn, René
AU - Vitart, Veronique
AU - Hewitt, Alex W.
AU - Oexle, Konrad
AU - Mäkelä, Kari Matti
AU - MacGregor, Stuart
AU - Pirastu, Mario
AU - Fan, Qiao
AU - Cheng, Ching Yu
AU - St Pourcain, Beaté
AU - McMahon, George
AU - Kemp, John P.
AU - Northstone, Kate
AU - Rahi, Jugnoo S.
AU - Cumberland, Phillippa M.
AU - Martin, Nicholas G.
AU - Sanfilippo, Paul G.
AU - Lu, Yi
AU - Wang, Ya Xing
AU - Hayward, Caroline
AU - Polašek, Ozren
AU - Campbell, Harry
AU - Bencic, Goran
AU - Wright, Alan F.
AU - Wedenoja, Juho
AU - Zeller, Tanja
AU - Schillert, Arne
AU - Mirshahi, Alireza
AU - Lackner, Karl
AU - Yip, Shea Ping
AU - Yap, Maurice K.H.
AU - Ried, Janina S.
AU - Gieger, Christian
AU - Murgia, Federico
AU - Wilson, James F.
AU - Fleck, Brian
AU - Yazar, Seyhan
AU - Vingerling, Johannes R.
AU - Hofman, Albert
AU - Uitterlinden, André
AU - Rivadeneira, Fernando
AU - Amin, Najaf
AU - Karssen, Lennart
AU - Meitinger, Thomas
N1 - Publisher Copyright:
© 2014, The Author(s).
PY - 2015/1/13
Y1 - 2015/1/13
N2 - To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged <25 years (4 cohorts, N = 5,640); and all independent individuals from the above three samples combined with a sample of Chinese subjects aged <25 years (N = 45,931). Participants were classified as cases with refractive astigmatism if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise. Genome-wide association analysis was carried out for each cohort separately using logistic regression. Meta-analysis was conducted using a fixed effects model. In the older European group the most strongly associated marker was downstream of the neurexin-1 (NRXN1) gene (rs1401327, P = 3.92E−8). No other region reached genome-wide significance, and association signals were lower for the younger European group and Asian group. In the meta-analysis of all cohorts, no marker reached genome-wide significance: The most strongly associated regions were, NRXN1 (rs1401327, P = 2.93E−07), TOX (rs7823467, P = 3.47E−07) and LINC00340 (rs12212674, P = 1.49E−06). For 34 markers identified in prior GWAS for spherical equivalent refractive error, the beta coefficients for genotype versus spherical equivalent, and genotype versus refractive astigmatism, were highly correlated (r = −0.59, P = 2.10E−04). This work revealed no consistent or strong genetic signals for refractive astigmatism; however, the TOX gene region previously identified in GWAS for spherical equivalent refractive error was the second most strongly associated region. Analysis of additional markers provided evidence supporting widespread genetic co-susceptibility for spherical and astigmatic refractive errors.
AB - To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged <25 years (4 cohorts, N = 5,640); and all independent individuals from the above three samples combined with a sample of Chinese subjects aged <25 years (N = 45,931). Participants were classified as cases with refractive astigmatism if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise. Genome-wide association analysis was carried out for each cohort separately using logistic regression. Meta-analysis was conducted using a fixed effects model. In the older European group the most strongly associated marker was downstream of the neurexin-1 (NRXN1) gene (rs1401327, P = 3.92E−8). No other region reached genome-wide significance, and association signals were lower for the younger European group and Asian group. In the meta-analysis of all cohorts, no marker reached genome-wide significance: The most strongly associated regions were, NRXN1 (rs1401327, P = 2.93E−07), TOX (rs7823467, P = 3.47E−07) and LINC00340 (rs12212674, P = 1.49E−06). For 34 markers identified in prior GWAS for spherical equivalent refractive error, the beta coefficients for genotype versus spherical equivalent, and genotype versus refractive astigmatism, were highly correlated (r = −0.59, P = 2.10E−04). This work revealed no consistent or strong genetic signals for refractive astigmatism; however, the TOX gene region previously identified in GWAS for spherical equivalent refractive error was the second most strongly associated region. Analysis of additional markers provided evidence supporting widespread genetic co-susceptibility for spherical and astigmatic refractive errors.
UR - https://www.scopus.com/pages/publications/84925501566
U2 - 10.1007/s00439-014-1500-y
DO - 10.1007/s00439-014-1500-y
M3 - Article
C2 - 25367360
AN - SCOPUS:84925501566
SN - 0340-6717
VL - 134
SP - 131
EP - 146
JO - Human Genetics
JF - Human Genetics
IS - 2
ER -