When do myopia genes have their effect? Comparison of genetic risks between children and adults.
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.
Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
J Willem L
JW
Tideman
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
Qiao
Q
Fan
Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Orthoptics, School of Applied Science Utrecht, Rotterdam, The Netherlands.
Jan Roelof
JR
Polling
Department of Statistical Science, School of Mathematics & Computational Science, Sun Yat-Sen University, Guangzhou, GD, China.|SYSU-CMU Shunde International Joint Research Institute, Guangzhou, GD, China.|Southern China Research Center of Statistical Science, Sun Yat-Sen University, Guangzhou, GD, China.
Xiaobo
X
Guo
Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia.
Seyhan
S
Yazar
Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.
Anthony
A
Khawaja
Department of Ophthalmology, University Medical Center, Mainz, Germany.|Department of Ophthalmology, Inselspital, Bern, Switzerland.
René
R
Höhn
Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Yi
Y
Lu
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Vincent W V
VW
Jaddoe
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Kenji
K
Yamashiro
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Munemitsu
M
Yoshikawa
Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center Mainz, Mainz, Germany.
Aslihan
A
Gerhold-Ay
Department of Ophthalmology, University Medical Center, Mainz, Germany.
Stefan
S
Nickels
Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany.
Tanja
T
Zeller
Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia.|State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Mingguang
M
He
Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Thibaud
T
Boutin
Department of Ophthalmology, Sisters of Mercy University Hospital, Zagreb, Croatia.
Goran
G
Bencic
Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Veronique
V
Vitart
Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia.
David A
DA
Mackey
NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust & UCL Institute of Ophthalmology, London, United Kingdom.
Paul J
PJ
Foster
Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Stuart
S
MacGregor
School of Social and Community Medicine, University of Bristol, Bristol, England.
Cathy
C
Williams
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.|National University of Singapore Saw Swee Hock School of Public Health, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
Seang Mei
SM
Saw
School of Optometry & Vision Sciences, Cardiff University, Cardiff, Wales.
Jeremy A
JA
Guggenheim
Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Caroline C W
CC
Klaver
Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.
D000293:Adolescent; D000328:Adult; D000483:Alleles; D001699:Biometry; D002648:Child; D017630:Connexins / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007797:Laminin / Q000235:genetics*; D008297:Male; D009216:Myopia / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult; D000097004:Gap Junction delta-2 Protein
D017630:Connexins; D007797:Laminin; D000097004:Gap Junction delta-2 Protein; C102645:laminin alpha 2
SNPs; development; genetic risk; myopia