When do myopia genes have their effect?: Comparison of genetic risks between children and adults

CREAM Consortium; J Willem L Tideman; Qiao Fan; Jan Roelof Polling; Xiaobo Guo; Seyhan Yazar; Anthony Khawaja; René Höhn; Yi Lu; Vincent W V Jaddoe; Kenji Yamashiro; Munemitsu Yoshikawa; Aslihan Gerhold-Ay; Stefan Nickels; Tanja Zeller; Mingguang He; Thibaud Boutin; Goran Bencic; Veronique Vitart; David A Mackey; Paul J Foster; Stuart MacGregor; Cathy Williams; Seang Mei Saw; Jeremy A Guggenheim; Caroline C W Klaver

doi:10.1002/gepi.21999

When do myopia genes have their effect? Comparison of genetic risks between children and adults

CREAM Consortium, J Willem L Tideman, Qiao Fan, Jan Roelof Polling, Xiaobo Guo, Seyhan Yazar, Anthony Khawaja, René Höhn, Yi Lu, Vincent W V Jaddoe, Kenji Yamashiro, Munemitsu Yoshikawa, Aslihan Gerhold-Ay, Stefan Nickels, Tanja Zeller, Mingguang He, Thibaud Boutin, Goran Bencic, Veronique Vitart, David A MackeyPaul J Foster, Stuart MacGregor, Cathy Williams, Seang Mei Saw, Jeremy A Guggenheim, Caroline C W Klaver

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

Abstract / Description of output

Previous studies have identified many genetic loci for refractive error and myopia. We aimed to investigate the effect of these loci on ocular biometry as a function of age in children, adolescents, and adults. The study population consisted of three age groups identified from the international CREAM consortium: 5,490 individuals aged <10 years; 5,000 aged 10-25 years; and 16,274 aged >25 years. All participants had undergone standard ophthalmic examination including measurements of axial length (AL) and corneal radius (CR). We examined the lead SNP at all 39 currently known genetic loci for refractive error identified from genome-wide association studies (GWAS), as well as a combined genetic risk score (GRS). The beta coefficient for association between SNP genotype or GRS versus AL/CR was compared across the three age groups, adjusting for age, sex, and principal components. Analyses were Bonferroni-corrected. In the age group <10 years, three loci (GJD2, CHRNG, ZIC2) were associated with AL/CR. In the age group 10-25 years, four loci (BMP2, KCNQ5, A2BP1, CACNA1D) were associated; and in adults 20 loci were associated. Association with GRS increased with age; β = 0.0016 per risk allele (P = 2 × 10(-8) ) in <10 years, 0.0033 (P = 5 × 10(-15) ) in 10- to 25-year-olds, and 0.0048 (P = 1 × 10(-72) ) in adults. Genes with strongest effects (LAMA2, GJD2) had an early effect that increased with age. Our results provide insights on the age span during which myopia genes exert their effect. These insights form the basis for understanding the mechanisms underlying high and pathological myopia.

Original language	English
Journal	Genetic Epidemiology
Volume	40
Issue number	8
Early online date	9 Sept 2016
DOIs	https://doi.org/10.1002/gepi.21999
Publication status	Published - Dec 2016

Access to Document

10.1002/gepi.21999

When do myopia genes have their effectAccepted author manuscript, 547 KBLicence: Creative Commons: Attribution Non-Commercial (CC-BY-NC)

Cite this

CREAM Consortium, Tideman, J. W. L., Fan, Q., Polling, J. R., Guo, X., Yazar, S., Khawaja, A., Höhn, R., Lu, Y., Jaddoe, V. W. V., Yamashiro, K., Yoshikawa, M., Gerhold-Ay, A., Nickels, S., Zeller, T., He, M., Boutin, T., Bencic, G., Vitart, V., ... Klaver, C. C. W. (2016). When do myopia genes have their effect? Comparison of genetic risks between children and adults. Genetic Epidemiology, 40(8). https://doi.org/10.1002/gepi.21999

@article{c9fd1574689747bebfca7671d14f0ec6,

title = "When do myopia genes have their effect?: Comparison of genetic risks between children and adults",

abstract = "Previous studies have identified many genetic loci for refractive error and myopia. We aimed to investigate the effect of these loci on ocular biometry as a function of age in children, adolescents, and adults. The study population consisted of three age groups identified from the international CREAM consortium: 5,490 individuals aged <10 years; 5,000 aged 10-25 years; and 16,274 aged >25 years. All participants had undergone standard ophthalmic examination including measurements of axial length (AL) and corneal radius (CR). We examined the lead SNP at all 39 currently known genetic loci for refractive error identified from genome-wide association studies (GWAS), as well as a combined genetic risk score (GRS). The beta coefficient for association between SNP genotype or GRS versus AL/CR was compared across the three age groups, adjusting for age, sex, and principal components. Analyses were Bonferroni-corrected. In the age group <10 years, three loci (GJD2, CHRNG, ZIC2) were associated with AL/CR. In the age group 10-25 years, four loci (BMP2, KCNQ5, A2BP1, CACNA1D) were associated; and in adults 20 loci were associated. Association with GRS increased with age; β = 0.0016 per risk allele (P = 2 × 10(-8) ) in <10 years, 0.0033 (P = 5 × 10(-15) ) in 10- to 25-year-olds, and 0.0048 (P = 1 × 10(-72) ) in adults. Genes with strongest effects (LAMA2, GJD2) had an early effect that increased with age. Our results provide insights on the age span during which myopia genes exert their effect. These insights form the basis for understanding the mechanisms underlying high and pathological myopia.",

author = "{CREAM Consortium} and Tideman, {J Willem L} and Qiao Fan and Polling, {Jan Roelof} and Xiaobo Guo and Seyhan Yazar and Anthony Khawaja and Ren{\'e} H{\"o}hn and Yi Lu and Jaddoe, {Vincent W V} and Kenji Yamashiro and Munemitsu Yoshikawa and Aslihan Gerhold-Ay and Stefan Nickels and Tanja Zeller and Mingguang He and Thibaud Boutin and Goran Bencic and Veronique Vitart and Mackey, {David A} and Foster, {Paul J} and Stuart MacGregor and Cathy Williams and Saw, {Seang Mei} and Guggenheim, {Jeremy A} and Klaver, {Caroline C W}",

note = "{\textcopyright} 2016 WILEY PERIODICALS, INC.",

year = "2016",

month = dec,

doi = "10.1002/gepi.21999",

language = "English",

volume = "40",

journal = "Genetic Epidemiology",

issn = "0741-0395",

publisher = "Wiley",

number = "8",

}

CREAM Consortium, Tideman, JWL, Fan, Q, Polling, JR, Guo, X, Yazar, S, Khawaja, A, Höhn, R, Lu, Y, Jaddoe, VWV, Yamashiro, K, Yoshikawa, M, Gerhold-Ay, A, Nickels, S, Zeller, T, He, M, Boutin, T, Bencic, G, Vitart, V, Mackey, DA, Foster, PJ, MacGregor, S, Williams, C, Saw, SM, Guggenheim, JA & Klaver, CCW 2016, 'When do myopia genes have their effect? Comparison of genetic risks between children and adults', Genetic Epidemiology, vol. 40, no. 8. https://doi.org/10.1002/gepi.21999

TY - JOUR

T1 - When do myopia genes have their effect?

T2 - Comparison of genetic risks between children and adults

AU - CREAM Consortium

AU - Tideman, J Willem L

AU - Fan, Qiao

AU - Polling, Jan Roelof

AU - Guo, Xiaobo

AU - Yazar, Seyhan

AU - Khawaja, Anthony

AU - Höhn, René

AU - Lu, Yi

AU - Jaddoe, Vincent W V

AU - Yamashiro, Kenji

AU - Yoshikawa, Munemitsu

AU - Gerhold-Ay, Aslihan

AU - Nickels, Stefan

AU - Zeller, Tanja

AU - He, Mingguang

AU - Boutin, Thibaud

AU - Bencic, Goran

AU - Vitart, Veronique

AU - Mackey, David A

AU - Foster, Paul J

AU - MacGregor, Stuart

AU - Williams, Cathy

AU - Saw, Seang Mei

AU - Guggenheim, Jeremy A

AU - Klaver, Caroline C W

PY - 2016/12

Y1 - 2016/12

N2 - Previous studies have identified many genetic loci for refractive error and myopia. We aimed to investigate the effect of these loci on ocular biometry as a function of age in children, adolescents, and adults. The study population consisted of three age groups identified from the international CREAM consortium: 5,490 individuals aged <10 years; 5,000 aged 10-25 years; and 16,274 aged >25 years. All participants had undergone standard ophthalmic examination including measurements of axial length (AL) and corneal radius (CR). We examined the lead SNP at all 39 currently known genetic loci for refractive error identified from genome-wide association studies (GWAS), as well as a combined genetic risk score (GRS). The beta coefficient for association between SNP genotype or GRS versus AL/CR was compared across the three age groups, adjusting for age, sex, and principal components. Analyses were Bonferroni-corrected. In the age group <10 years, three loci (GJD2, CHRNG, ZIC2) were associated with AL/CR. In the age group 10-25 years, four loci (BMP2, KCNQ5, A2BP1, CACNA1D) were associated; and in adults 20 loci were associated. Association with GRS increased with age; β = 0.0016 per risk allele (P = 2 × 10(-8) ) in <10 years, 0.0033 (P = 5 × 10(-15) ) in 10- to 25-year-olds, and 0.0048 (P = 1 × 10(-72) ) in adults. Genes with strongest effects (LAMA2, GJD2) had an early effect that increased with age. Our results provide insights on the age span during which myopia genes exert their effect. These insights form the basis for understanding the mechanisms underlying high and pathological myopia.

AB - Previous studies have identified many genetic loci for refractive error and myopia. We aimed to investigate the effect of these loci on ocular biometry as a function of age in children, adolescents, and adults. The study population consisted of three age groups identified from the international CREAM consortium: 5,490 individuals aged <10 years; 5,000 aged 10-25 years; and 16,274 aged >25 years. All participants had undergone standard ophthalmic examination including measurements of axial length (AL) and corneal radius (CR). We examined the lead SNP at all 39 currently known genetic loci for refractive error identified from genome-wide association studies (GWAS), as well as a combined genetic risk score (GRS). The beta coefficient for association between SNP genotype or GRS versus AL/CR was compared across the three age groups, adjusting for age, sex, and principal components. Analyses were Bonferroni-corrected. In the age group <10 years, three loci (GJD2, CHRNG, ZIC2) were associated with AL/CR. In the age group 10-25 years, four loci (BMP2, KCNQ5, A2BP1, CACNA1D) were associated; and in adults 20 loci were associated. Association with GRS increased with age; β = 0.0016 per risk allele (P = 2 × 10(-8) ) in <10 years, 0.0033 (P = 5 × 10(-15) ) in 10- to 25-year-olds, and 0.0048 (P = 1 × 10(-72) ) in adults. Genes with strongest effects (LAMA2, GJD2) had an early effect that increased with age. Our results provide insights on the age span during which myopia genes exert their effect. These insights form the basis for understanding the mechanisms underlying high and pathological myopia.

U2 - 10.1002/gepi.21999

DO - 10.1002/gepi.21999

M3 - Article

C2 - 27611182

SN - 0741-0395

VL - 40

JO - Genetic Epidemiology

JF - Genetic Epidemiology

IS - 8

ER -

When do myopia genes have their effect? Comparison of genetic risks between children and adults

Abstract / Description of output

Access to Document

Fingerprint

Cite this