When do myopia genes have their effect? Comparison of genetic risks between children and adults
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When do myopia genes have their effect? Comparison of genetic risks between children and adults. / Tideman, J Willem L; Fan, Qiao; Polling, Jan Roelof; Guo, Xiaobo; Yazar, Seyhan; Khawaja, Anthony; Höhn, René; Lu, Yi; Jaddoe, Vincent W V; Yamashiro, Kenji; Yoshikawa, Munemitsu; Gerhold-Ay, Aslihan; Nickels, Stefan; Zeller, Tanja; He, Mingguang; Boutin, Thibaud; Bencic, Goran; Vitart, Veronique; Mackey, David A; Foster, Paul J; MacGregor, Stuart; Williams, Cathy; Saw, Seang Mei; Guggenheim, Jeremy A; Klaver, Caroline C W; CREAM Consortium.
In: GENET EPIDEMIOL, Vol. 40, No. 8, 12.2016, p. 756-766.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - When do myopia genes have their effect? Comparison of genetic risks between children and adults
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
AU - CREAM Consortium
N1 - © 2016 WILEY PERIODICALS, INC.
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.
KW - Adolescent
KW - Adult
KW - Alleles
KW - Biometry
KW - Child
KW - Connexins/genetics
KW - Female
KW - Genetic Loci
KW - Genome-Wide Association Study
KW - Genotype
KW - Humans
KW - Laminin/genetics
KW - Male
KW - Myopia/genetics
KW - Polymorphism, Single Nucleotide/genetics
KW - Risk Factors
KW - Young Adult
U2 - 10.1002/gepi.21999
DO - 10.1002/gepi.21999
M3 - SCORING: Journal article
C2 - 27611182
VL - 40
SP - 756
EP - 766
JO - GENET EPIDEMIOL
JF - GENET EPIDEMIOL
SN - 0741-0395
IS - 8
ER -