Dataset Information

Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium.

ABSTRACT: Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations. The study population comprised 31 cohorts from the Consortium of Refractive Error and Myopia (CREAM) representing 4 different continents with 55,177 individuals; 42,845 Caucasians and 12,332 Asians. We performed a meta-analysis of 14 single nucleotide polymorphisms (SNPs) on 15q14 and 5 SNPs on 15q25 using linear regression analysis with spherical equivalent as a quantitative outcome, adjusted for age and sex. We calculated the odds ratio (OR) of myopia versus hyperopia for carriers of the top-SNP alleles using a fixed effects meta-analysis. At locus 15q14, all SNPs were significantly replicated, with the lowest P value 3.87 × 10(-12) for SNP rs634990 in Caucasians, and 9.65 × 10(-4) for rs8032019 in Asians. The overall meta-analysis provided P value 9.20 × 10(-23) for the top SNP rs634990. The risk of myopia versus hyperopia was OR 1.88 (95 % CI 1.64, 2.16, P < 0.001) for homozygous carriers of the risk allele at the top SNP rs634990, and OR 1.33 (95 % CI 1.19, 1.49, P < 0.001) for heterozygous carriers. SNPs at locus 15q25 did not replicate significantly (P value 5.81 × 10(-2) for top SNP rs939661). We conclude that common variants at chromosome 15q14 influence susceptibility for myopia in Caucasian and Asian populations world-wide.

SUBMITTER: Verhoeven VJ

PROVIDER: S-EPMC3418496 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium.

Verhoeven Virginie J M VJ Hysi Pirro G PG Saw Seang-Mei SM Vitart Veronique V Mirshahi Alireza A Guggenheim Jeremy A JA Cotch Mary Frances MF Yamashiro Kenji K Baird Paul N PN Mackey David A DA Wojciechowski Robert R Ikram M Kamran MK Hewitt Alex W AW Duggal Priya P Janmahasatian Sarayut S Khor Chiea-Chuen CC Fan Qiao Q Zhou Xin X Young Terri L TL Tai E-Shyong ES Goh Liang-Kee LK Li Yi-Ju YJ Aung Tin T Vithana Eranga E Teo Yik-Ying YY Tay Wanting W Sim Xueling X Rudan Igor I Hayward Caroline C Wright Alan F AF Polasek Ozren O Campbell Harry H Wilson James F JF Fleck Brian W BW Nakata Isao I Yoshimura Nagahisa N Yamada Ryo R Matsuda Fumihiko F Ohno-Matsui Kyoko K Nag Abhishek A McMahon George G St Pourcain Beate B Lu Yi Y Rahi Jugnoo S JS Cumberland Phillippa M PM Bhattacharya Shomi S Simpson Claire L CL Atwood Larry D LD Li Xiaohui X Raffel Leslie J LJ Murgia Federico F Portas Laura L Despriet Dominiek D G DD van Koolwijk Leonieke M E LM Wolfram Christian C Lackner Karl J KJ Tönjes Anke A Mägi Reedik R Lehtimäki Terho T Kähönen Mika M Esko Tõnu T Metspalu Andres A Rantanen Taina T Pärssinen Olavi O Klein Barbara E BE Meitinger Thomas T Spector Timothy D TD Oostra Ben A BA Smith Albert V AV de Jong Paulus T V M PT Hofman Albert A Amin Najaf N Karssen Lennart C LC Rivadeneira Fernando F Vingerling Johannes R JR Eiríksdóttir Guðný G Gudnason Vilmundur V Döring Angela A Bettecken Thomas T Uitterlinden André G AG Williams Cathy C Zeller Tanja T Castagné Raphaële R Oexle Konrad K van Duijn Cornelia M CM Iyengar Sudha K SK Mitchell Paul P Wang Jie Jin JJ Höhn René R Pfeiffer Norbert N Bailey-Wilson Joan E JE Stambolian Dwight D Wong Tien-Yin TY Hammond Christopher J CJ Klaver Caroline C W CC

Human genetics 20120605 9

Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations. The study population comprised 31 cohorts from the Consortium of Refractive Error and Myopia (CRE ...[more]

PMID: 22665138

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Project description:The Cancer Vaccine Consortium of the Sabin Vaccine Institute (CVC/SVI) is conducting an ongoing large-scale immune monitoring harmonization program through its members and affiliated associations. This effort was brought to life as an external validation program by conducting an international Elispot proficiency panel with 36 laboratories in 2005, and was followed by a second panel with 29 participating laboratories in 2006 allowing for application of learnings from the first panel. Critical protocol choices, as well as standardization and validation practices among laboratories were assessed through detailed surveys. Although panel participants had to follow general guidelines in order to allow comparison of results, each laboratory was able to use its own protocols, materials and reagents. The second panel recorded an overall significantly improved performance, as measured by the ability to detect all predefined responses correctly. Protocol choices and laboratory practices, which can have a dramatic effect on the overall assay outcome, were identified and lead to the following recommendations: (A) Establish a laboratory SOP for Elispot testing procedures including (A1) a counting method for apoptotic cells for determining adequate cell dilution for plating, and (A2) overnight rest of cells prior to plating and incubation, (B) Use only pre-tested serum optimized for low background: high signal ratio, (C) Establish a laboratory SOP for plate reading including (C1) human auditing during the reading process and (C2) adequate adjustments for technical artifacts, and (D) Only allow trained personnel, which is certified per laboratory SOPs to conduct assays. Recommendations described under (A) were found to make a statistically significant difference in assay performance, while the remaining recommendations are based on practical experiences confirmed by the panel results, which could not be statistically tested. These results provide initial harmonization guidelines to optimize Elispot assay performance to the immunotherapy community. Further optimization is in process with ongoing panels.

Project description:BackgroundThe polymorphisms rs6885224 and rs634990 have been reported to be associated with high myopia in many populations. As there is still no report on whether these two SNPs are associated with myopia in the Tujia and Miao minority areas of China, we conducted a replication study to evaluate the association of single-nucleotide polymorphisms in the regions 5p15.2 and 15q14 with high myopia in Tujia and Miao Chinese populations.MethodsWe performed a comprehensive meta-analysis of 5831 cases and 7055 controls to assess whether rs6885224 in the 5p15.2 region and rs634990 in the 15q14 region are associated with high myopia. Our replication study enrolled 804 individuals. Genomic DNA was extracted from venous leukocytes, and these two SNPs were genotyped by Sanger sequencing. Allele and genotype frequencies were analysed using χ2 tests, and ORs and 95% CIs were calculated.ResultsAccording to the results of the meta-analysis, rs6885224 in the CTNND2 gene showed no association with myopia [p = 0.222, OR = 1.154, 95% CI (0.917-1.452)]. Conversely, rs634990 in the 15q14 region did exhibit a significant correlation with myopia [p = 7.270 × 10- 7, OR = 0.817, 95% CI (0.754-0.885)]. In our replication study, no association with high myopia in the Tujia and Miao populations was found for rs634990 or rs6885224. The following were obtained by allele frequency analysis: rs6885224, p = 0.175, OR = 0.845, and 95% CI = 0.662-1.078; rs634990, p = 0.087, OR = 0.84, and the 95% CI = 0.687-1.026. Genotype frequency analysis yielded p = 0.376 for rs6885224 and p = 0.243 for rs634990.ConclusionsOur meta-analysis results show that rs634990 was significantly associated with myopia but that rs6885224 was not. Nevertheless, in our replication study, these two SNPs showed no association with myopia in the Tujia and Miao Chinese populations. This is the first report involving Tujia and Miao ethnic groups from Enshi minority areas. However, the sample size needs to be expanded and more stringent inclusion and exclusion criteria need to be formulated to verify the findings.

Dataset Information

Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium.

Publications

Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium.

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