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

Q Li; R Wojciechowski; CL Simpson; PG Hysi; Virginie Verhoeven; MK Ikram; R Hohn; V Vitart; AW Hewitt; K Oexle; KM Makela; S Macgregor; M Pirastu; Q Fan; CY (Ching-Yu) Cheng; B St Pourcain; G McMahon; JP Kemp; K Northstone; JS Rahi; PM Cumberland; NG Martin; PG Sanfilippo; Y (Yi) Lu; YX Wang; C Hayward; O Polasek; H Campbell; G Bencic; AF Wright; J Wedenoja; T Zeller; A Schillert; A Mirshahi; K Lackner; SP Yip; MKH Yap; JS Ried; C Gieger; F Murgia; JF Wilson; B Fleck; S Yazar; Hans Vingerling; Bert Hofman; André Uitterlinden; Fernando Rivadeneira; Najaf Amin; L Karssen; Ben Oostra; X Zhou; YY Teo; ES Tai; E Vithana; V Barathi; YF Zheng; RG Siantar; K Neelam; YC Shin; J (Jan) Lam; E Yonova-Doing; C Venturini; SM Hosseini; HS Wong; T Lehtimaki; M Kahonen; O Raitakari; NJ Timpson; DM Evans; CC Khor; T Aung; TL Young; P Mitchell; B Klein; Cornelia Duijn; T Meitinger; JB Jonas; PN Baird; DA Mackey; TY Wong; SM Saw; O Parssinen; D Stambolian; CJ Hammond; Caroline Klaver; C Williams; AD Paterson; JE Bailey-Wilson; JA Guggenheim

doi: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

Q Li
, R Wojciechowski
, CL Simpson
, PG Hysi
, Virginie Verhoeven
, MK Ikram
, R Hohn
, V Vitart
, AW Hewitt
, K Oexle
, KM Makela
, S Macgregor
, M Pirastu
, Q Fan
, CY (Ching-Yu) Cheng
, B St Pourcain
, G McMahon
, JP Kemp
, K Northstone
, JS Rahi

PM Cumberland, NG Martin, PG Sanfilippo, Y (Yi) Lu, YX Wang, C Hayward, O Polasek, H Campbell, G Bencic, AF Wright, J Wedenoja, T Zeller, A Schillert, A Mirshahi, K Lackner, SP Yip, MKH Yap, JS Ried, C Gieger, F Murgia, JF Wilson, B Fleck, S Yazar, Hans Vingerling, Bert Hofman, André Uitterlinden, Fernando Rivadeneira, Najaf Amin, L Karssen, Ben Oostra, X Zhou, YY Teo, ES Tai, E Vithana, V Barathi, YF Zheng, RG Siantar, K Neelam, YC Shin, J (Jan) Lam, E Yonova-Doing, C Venturini, SM Hosseini, HS Wong, T Lehtimaki, M Kahonen, O Raitakari, NJ Timpson, DM Evans, CC Khor, T Aung, TL Young, P Mitchell, B Klein, Cornelia Duijn, T Meitinger, JB Jonas, PN Baird, DA Mackey, TY Wong, SM Saw, O Parssinen, D Stambolian, CJ Hammond, Caroline Klaver, C Williams, AD Paterson, JE Bailey-Wilson, JA Guggenheim

External organisation

Research output: Contribution to journal › Article › Academic › peer-review

30 Citations (Scopus)

32 Downloads (Pure)

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.

Original language	Undefined/Unknown
Pages (from-to)	131-146
Number of pages	16
Journal	Human Genetics
Volume	134
Issue number	2
DOIs	https://doi.org/10.1007/s00439-014-1500-y
Publication status	Published - 2015

Research programs

EMC MGC-02-96-01
EMC MM-01-39-09-A
EMC NIHES-01-64-01
EMC OR-01-60-01

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Cite this

Li, Q., Wojciechowski, R., Simpson, CL., Hysi, PG., Verhoeven, V., Ikram, MK., Hohn, R., Vitart, V., Hewitt, AW., Oexle, K., Makela, KM., Macgregor, S., Pirastu, M., Fan, Q., Cheng, CY., St Pourcain, B., McMahon, G., Kemp, JP., Northstone, K., ... Guggenheim, JA. (2015). Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium. Human Genetics, 134(2), 131-146. https://doi.org/10.1007/s00439-014-1500-y

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

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.",

author = "Q Li and R Wojciechowski and CL Simpson and PG Hysi and Virginie Verhoeven and MK Ikram and R Hohn and V Vitart and AW Hewitt and K Oexle and KM Makela and S Macgregor and M Pirastu and Q Fan and Cheng, \{CY (Ching-Yu)\} and \{St Pourcain\}, B and G McMahon and JP Kemp and K Northstone and JS Rahi and PM Cumberland and NG Martin and PG Sanfilippo and Lu, \{Y (Yi)\} and YX Wang and C Hayward and O Polasek and H Campbell and G Bencic and AF Wright and J Wedenoja and T Zeller and A Schillert and A Mirshahi and K Lackner and SP Yip and MKH Yap and JS Ried and C Gieger and F Murgia and JF Wilson and B Fleck and S Yazar and Hans Vingerling and Bert Hofman and Andr{\'e} Uitterlinden and Fernando Rivadeneira and Najaf Amin and L Karssen and Ben Oostra and X Zhou and YY Teo and ES Tai and E Vithana and V Barathi and YF Zheng and RG Siantar and K Neelam and YC Shin and Lam, \{J (Jan)\} and E Yonova-Doing and C Venturini and SM Hosseini and HS Wong and T Lehtimaki and M Kahonen and O Raitakari and NJ Timpson and DM Evans and CC Khor and T Aung and TL Young and P Mitchell and B Klein and Cornelia Duijn and T Meitinger and JB Jonas and PN Baird and DA Mackey and TY Wong and SM Saw and O Parssinen and D Stambolian and CJ Hammond and Caroline Klaver and C Williams and AD Paterson and JE Bailey-Wilson and JA Guggenheim",

year = "2015",

doi = "10.1007/s00439-014-1500-y",

language = "Undefined/Unknown",

volume = "134",

pages = "131--146",

journal = "Human Genetics",

issn = "0340-6717",

publisher = "Springer Science+Business Media",

number = "2",

}

Li, Q, Wojciechowski, R, Simpson, CL, Hysi, PG, Verhoeven, V, Ikram, MK, Hohn, R, Vitart, V, Hewitt, AW, Oexle, K, Makela, KM, Macgregor, S, Pirastu, M, Fan, Q, Cheng, CY, St Pourcain, B, McMahon, G, Kemp, JP, Northstone, K, Rahi, JS, Cumberland, PM, Martin, NG, Sanfilippo, PG, Lu, Y, Wang, YX, Hayward, C, Polasek, 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, H , Hofman, B, Uitterlinden, A, Rivadeneira, F, Amin, N, Karssen, L, Oostra, B, Zhou, X, Teo, YY, Tai, ES, Vithana, E, Barathi, V, Zheng, YF, Siantar, RG, Neelam, K, Shin, YC, Lam, J, Yonova-Doing, E, Venturini, C, Hosseini, SM, Wong, HS, Lehtimaki, T, Kahonen, M, Raitakari, O, Timpson, NJ, Evans, DM, Khor, CC, Aung, T, Young, TL, Mitchell, P, Klein, B, Duijn, C, Meitinger, T, Jonas, JB, Baird, PN, Mackey, DA, Wong, TY, Saw, SM, Parssinen, O, Stambolian, D, Hammond, CJ, Klaver, C, Williams, C, Paterson, AD, Bailey-Wilson, JE & Guggenheim, JA 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. 131-146. https://doi.org/10.1007/s00439-014-1500-y

TY - JOUR

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

AU - Li, Q

AU - Wojciechowski, R

AU - Simpson, CL

AU - Hysi, PG

AU - Verhoeven, Virginie

AU - Ikram, MK

AU - Hohn, R

AU - Vitart, V

AU - Hewitt, AW

AU - Oexle, K

AU - Makela, KM

AU - Macgregor, S

AU - Pirastu, M

AU - Fan, Q

AU - Cheng, CY (Ching-Yu)

AU - St Pourcain, B

AU - McMahon, G

AU - Kemp, JP

AU - Northstone, K

AU - Rahi, JS

AU - Cumberland, PM

AU - Martin, NG

AU - Sanfilippo, PG

AU - Lu, Y (Yi)

AU - Wang, YX

AU - Hayward, C

AU - Polasek, O

AU - Campbell, H

AU - Bencic, G

AU - Wright, AF

AU - Wedenoja, J

AU - Zeller, T

AU - Schillert, A

AU - Mirshahi, A

AU - Lackner, K

AU - Yip, SP

AU - Yap, MKH

AU - Ried, JS

AU - Gieger, C

AU - Murgia, F

AU - Wilson, JF

AU - Fleck, B

AU - Yazar, S

AU - Vingerling, Hans

AU - Hofman, Bert

AU - Uitterlinden, André

AU - Rivadeneira, Fernando

AU - Amin, Najaf

AU - Karssen, L

AU - Oostra, Ben

AU - Zhou, X

AU - Teo, YY

AU - Tai, ES

AU - Vithana, E

AU - Barathi, V

AU - Zheng, YF

AU - Siantar, RG

AU - Neelam, K

AU - Shin, YC

AU - Lam, J (Jan)

AU - Yonova-Doing, E

AU - Venturini, C

AU - Hosseini, SM

AU - Wong, HS

AU - Lehtimaki, T

AU - Kahonen, M

AU - Raitakari, O

AU - Timpson, NJ

AU - Evans, DM

AU - Khor, CC

AU - Aung, T

AU - Young, TL

AU - Mitchell, P

AU - Klein, B

AU - Duijn, Cornelia

AU - Meitinger, T

AU - Jonas, JB

AU - Baird, PN

AU - Mackey, DA

AU - Wong, TY

AU - Saw, SM

AU - Parssinen, O

AU - Stambolian, D

AU - Hammond, CJ

AU - Klaver, Caroline

AU - Williams, C

AU - Paterson, AD

AU - Bailey-Wilson, JE

AU - Guggenheim, JA

PY - 2015

Y1 - 2015

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.

U2 - 10.1007/s00439-014-1500-y

DO - 10.1007/s00439-014-1500-y

M3 - Article

C2 - 25367360

SN - 0340-6717

VL - 134

SP - 131

EP - 146

JO - Human Genetics

JF - Human Genetics

IS - 2

ER -