Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium
Standard
Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium. / Li, Qing; Wojciechowski, Robert; Simpson, Claire L; Hysi, Pirro G; Verhoeven, Virginie J M; Ikram, Mohammad Kamran; Höhn, René; Vitart, Veronique; Hewitt, Alex W; Oexle, Konrad; Mäkelä, Kari-Matti; MacGregor, Stuart; Pirastu, Mario; Fan, Qiao; Cheng, Ching-Yu; St Pourcain, Beaté; McMahon, George; Kemp, John P; Northstone, Kate; Rahi, Jugnoo S; Cumberland, Phillippa M; Martin, Nicholas G; Sanfilippo, Paul G; Lu, Yi; Wang, Ya Xing; Hayward, Caroline; Polašek, Ozren; Campbell, Harry; Bencic, Goran; Wright, Alan F; Wedenoja, Juho; Zeller, Tanja; Schillert, Arne; Mirshahi, Alireza; Lackner, Karl; Yip, Shea Ping; Yap, Maurice K H; Ried, Janina S; Gieger, Christian; Murgia, Federico; Wilson, James F; Fleck, Brian; Yazar, Seyhan; Vingerling, Johannes R; Hofman, Albert; Uitterlinden, André; Rivadeneira, Fernando; Amin, Najaf; Karssen, Lennart; Oostra, Ben A; Zhou, Xin; Teo, Yik-Ying; Tai, E Shyong; Vithana, Eranga; Barathi, Veluchamy; Zheng, Yingfeng; Siantar, Rosalynn Grace; Neelam, Kumari; Shin, Youchan; Lam, Janice; Yonova-Doing, Ekaterina; Venturini, Cristina; Hosseini, S Mohsen; Wong, Hoi-Suen; Lehtimäki, Terho; Kähönen, Mika; Raitakari, Olli; Timpson, Nicholas J; Evans, David M; Khor, Chiea-Chuen; Aung, Tin; Young, Terri L; Mitchell, Paul; Klein, Barbara; van Duijn, Cornelia M; Meitinger, Thomas; Jonas, Jost B; Baird, Paul N; Mackey, David A; Wong, Tien Yin; Saw, Seang-Mei; Pärssinen, Olavi; Stambolian, Dwight; Hammond, Christopher J; Klaver, Caroline C W; Williams, Cathy; Paterson, Andrew D; Bailey-Wilson, Joan E; Guggenheim, Jeremy A; CREAM Consortium.
In: HUM GENET, Vol. 134, No. 2, 02.2015, p. 131-146.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: 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 - Oostra, Ben A
AU - Zhou, Xin
AU - Teo, Yik-Ying
AU - Tai, E Shyong
AU - Vithana, Eranga
AU - Barathi, Veluchamy
AU - Zheng, Yingfeng
AU - Siantar, Rosalynn Grace
AU - Neelam, Kumari
AU - Shin, Youchan
AU - Lam, Janice
AU - Yonova-Doing, Ekaterina
AU - Venturini, Cristina
AU - Hosseini, S Mohsen
AU - Wong, Hoi-Suen
AU - Lehtimäki, Terho
AU - Kähönen, Mika
AU - Raitakari, Olli
AU - Timpson, Nicholas J
AU - Evans, David M
AU - Khor, Chiea-Chuen
AU - Aung, Tin
AU - Young, Terri L
AU - Mitchell, Paul
AU - Klein, Barbara
AU - van Duijn, Cornelia M
AU - Meitinger, Thomas
AU - Jonas, Jost B
AU - Baird, Paul N
AU - Mackey, David A
AU - Wong, Tien Yin
AU - Saw, Seang-Mei
AU - Pärssinen, Olavi
AU - Stambolian, Dwight
AU - Hammond, Christopher J
AU - Klaver, Caroline C W
AU - Williams, Cathy
AU - Paterson, Andrew D
AU - Bailey-Wilson, Joan E
AU - Guggenheim, Jeremy A
AU - CREAM Consortium
PY - 2015/2
Y1 - 2015/2
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.
KW - Adult
KW - Age Factors
KW - Asian Continental Ancestry Group
KW - Astigmatism/genetics
KW - Calcium-Binding Proteins
KW - Cell Adhesion Molecules, Neuronal/genetics
KW - Cohort Studies
KW - European Continental Ancestry Group
KW - Female
KW - Genetic Markers
KW - Genome-Wide Association Study
KW - High Mobility Group Proteins/genetics
KW - Humans
KW - Male
KW - Middle Aged
KW - Nerve Tissue Proteins/genetics
KW - Neural Cell Adhesion Molecules
U2 - 10.1007/s00439-014-1500-y
DO - 10.1007/s00439-014-1500-y
M3 - SCORING: Journal article
C2 - 25367360
VL - 134
SP - 131
EP - 146
JO - HUM GENET
JF - HUM GENET
SN - 0340-6717
IS - 2
ER -