Meta-analysis of gene–environment-wide association scans accounting for education level identifies additional loci for refractive error

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10(-5)), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia

Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia : The CREAM Consortium

Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).Peer reviewe

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

Peer reviewe

The genetics of myopia

Myopia is the most common eye condition worldwide and its prevalence is increasing. While changes in environment, such as time spent outdoors, have driven myopia rates, within populations myopia is highly heritable. Genes are estimated to explain up to 80% of the variance in refractive error. Initial attempts to identify myopia genes relied on family studies using linkage analysis or candidate gene approaches with limited progress. More genome-wide association study (GWAS) approaches have taken over, ultimately resulting in the identification of hundreds of genes for refractive error and myopia, providing new insights into its molecular machinery. These studies showed myopia is a complex trait, with many genetic variants of small effect influencing retinal signaling, eye growth and the normal process of emmetropization. The genetic architecture and its molecular mechanisms are still to be clarified and while genetic risk score prediction models are improving, this knowledge must be expanded to have impact on clinical practice

Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error

Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP x education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P <8.5 x 10(-5)), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.Peer reviewe

Study Of Nitriding The Iron Alloy Crsiv To Improve The Resistance To Fatigue From Bending [estudo Da Nitretação Na Liga Ferrosa Crsiv Para Melhorar A Resistencia A Fadiga Por Flexao Rotativa]

The present work shows the results reached to increase the resistance for bending fatigue through a nitriding cycle for wire used in the production of springs with 4mm of diameter and constituted of the ferrous league CrSiV - ASTM A878, marks Villares VIL878B - manufactured by the Aços Villares, unit of Sorocaba, SP. The curve of Wholer obtained for the nitriding wire, by especially device developed by the wires manufactures to springs manufactures, denominated "Nakamura Test ", is compared with the same component whit shot peening and without nitriding. The nitriding cycle will have as objective, besides the increase of the useful life of the springs, the maintenance of the mechanical properties of the base metal, because the treatment temperature used it is low in relation to the tempering temperature used for this material in this application. The optimization of the nitriding cycle includes the accomplishment of a uniform layer of diffusion of small thickness, besides the reduction of the white layer at minimum levels.33813390Bloem, L., Vendramim, J.C., Vatavuk, J., Estudo Comparativo Entre os Processes de Nitrocarbonetação em Banho de sal e por Plasma para Aplicação em Êmbolos, , SAE Brasil, 2000-01-3175Jack, D.H., Jack, K.H., (1973) Invited Review: Carbides and Nitrides in Steel Materials Science and Engineering, 11, p. 1027Liliental, W.K., Potencial Gas Nitriding(1986) Atlas of Fatigue Curve, , Metals Park, Ohio, OH 44073Koyasu, Y., Yanase, M., Nakano, O., Izawa, Y., Onada, M., Development of high fatigue strength spring steel (1996) Wire Journal International, pp. 88-91. , mayGenel, K., Demirkol, M., Çapa, M., Effects of ion nitriding on fatigue behaviour of AISI 4140 steel (2000) Materials Science & Engineering A, A279, pp. 207-216Forrest, P.G., (1970) Fatigue of Metals, pp. 192-193. , Oxford, Londo