Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium

Qing Li, Robert Wojciechowski, Claire L Simpson, Pirro G Hysi, Virginie J M Verhoeven, Mohammad Kamran Ikram, René Höhn, Veronique Vitart, Alex W Hewitt, Konrad Oexle, Kari-Matti Mäkelä, Stuart MacGregor, Mario Pirastu, Qiao Fan, Ching-Yu Cheng, Beaté St Pourcain, George McMahon, John P Kemp, Kate Northstone, Jugnoo S Rahi & 31 others Phillippa M Cumberland, Nicholas G Martin, Paul G Sanfilippo, Yi Lu, Ya Xing Wang, Caroline Hayward, Ozren Polašek, Harry Campbell, Goran Bencic, Alan F Wright, Juho Wedenoja, Tanja Zeller, Arne Schillert, Alireza Mirshahi, Karl Lackner, Shea Ping Yip, Maurice K H Yap, Janina S Ried, Christian Gieger, Federico Murgia, James F Wilson, Brian Fleck, Seyhan Yazar, Johannes R Vingerling, Albert Hofman, André Uitterlinden, Fernando Rivadeneira, Najaf Amin, Lennart Karssen, Ben A Oostra, CREAM Consortium

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

LanguageEnglish
Pages131-46
Number of pages16
JournalHuman Genetics
Volume134
Issue number2
DOIs
Publication statusPublished - Feb 2015
Externally publishedYes

Keywords

  • Adult
  • Age Factors
  • Asian Continental Ancestry Group
  • Astigmatism
  • Cell Adhesion Molecules, Neuronal
  • Cohort Studies
  • European Continental Ancestry Group
  • Female
  • Genetic Markers
  • Genome-Wide Association Study
  • High Mobility Group Proteins
  • Humans
  • Male
  • Middle Aged
  • Nerve Tissue Proteins
  • Journal Article
  • Meta-Analysis

Cite this

Li, Q., Wojciechowski, R., Simpson, C. L., Hysi, P. G., Verhoeven, V. J. M., Ikram, M. K., ... CREAM Consortium (2015). Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium. Human Genetics, 134(2), 131-46. https://doi.org/10.1007/s00439-014-1500-y
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 ; CREAM Consortium. / Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error : the CREAM consortium. In: Human Genetics. 2015 ; Vol. 134, No. 2. pp. 131-46.
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abstract = "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.",
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Li, Q, Wojciechowski, R, Simpson, CL, Hysi, PG, Verhoeven, VJM, Ikram, MK, Höhn, R, Vitart, V, Hewitt, AW, Oexle, K, Mäkelä, K-M, MacGregor, S, Pirastu, M, Fan, Q, Cheng, C-Y, St Pourcain, B, McMahon, G, Kemp, JP, Northstone, K, Rahi, JS, Cumberland, PM, Martin, NG, Sanfilippo, PG, Lu, Y, Wang, YX, Hayward, C, Polašek, O, Campbell, H, Bencic, G, Wright, AF, Wedenoja, J, Zeller, T, Schillert, A, Mirshahi, A, Lackner, K, Yip, SP, Yap, MKH, Ried, JS, Gieger, C, Murgia, F, Wilson, JF, Fleck, B, Yazar, S, Vingerling, JR, Hofman, A, Uitterlinden, A, Rivadeneira, F, Amin, N, Karssen, L, Oostra, BA & CREAM Consortium 2015, 'Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium', Human Genetics, vol. 134, no. 2, pp. 131-46. https://doi.org/10.1007/s00439-014-1500-y

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; CREAM Consortium.

In: Human Genetics, Vol. 134, No. 2, 02.2015, p. 131-46.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error

T2 - Human Genetics

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 - 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

KW - Cell Adhesion Molecules, Neuronal

KW - Cohort Studies

KW - European Continental Ancestry Group

KW - Female

KW - Genetic Markers

KW - Genome-Wide Association Study

KW - High Mobility Group Proteins

KW - Humans

KW - Male

KW - Middle Aged

KW - Nerve Tissue Proteins

KW - Journal Article

KW - Meta-Analysis

U2 - 10.1007/s00439-014-1500-y

DO - 10.1007/s00439-014-1500-y

M3 - Article

VL - 134

SP - 131

EP - 146

JO - Human Genetics

JF - Human Genetics

SN - 0340-6717

IS - 2

ER -