10 research outputs found
Retinal microvascular abnormalities and risk of renal failure in Asian populations
10.1371/journal.pone.0118076PLoS ONE102e011807
Insights into the Genetic Architecture of Early Stage Age-Related Macular Degeneration: A Genome-Wide Association Study Meta-Analysis
10.1371/journal.pone.0053830PLoS ONE81
Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium
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. © The Author(s) 2012
Prevalence and risk factors for peripheral artery disease in an Asian population with diabetes mellitus
We describe the prevalence and risk factors for PAD in Asian Malays with diabetes. A population-based study of 3,280 (78.7% response) Malay persons aged 40-80 years in Singapore was conducted. ABI was measured in all participants with a history of diabetes (N=634). PAD was defined to be present if ABI ≤ 0.9. All participants had standardised interviews, clinical examinations and laboratory investigation for risk factor assessment. The crude prevalence of PAD was 10.4% (95% CI: 8.3%-13.0%). After age standardisation to the 2000 Singapore Census population, the prevalence was 5% (95% CI: 3.8-8.6). In multivariate analyses, the presence of PAD was associated with older age (OR 1.05; 95% CI: 1.01-1.09, per year increase), female gender (OR 4.18; 95% CI: 1.67-10.43), cigarette smoking (OR 2.55; 95% CI: 1.05-6.20), higher systolic blood pressure (OR 1.28; 95% CI: 1.13-1.45), a history of myocardial infarction (OR 3.69; 95% CI: 1.79-7.61) and stroke (OR 3.06 95% CI: 1.25-7.50). In this Asian Malay population with diabetes, we found a high prevalence of PAD. The major risk factors for PAD among persons with diabetes are similar to studies in Caucasian populations, suggesting that strategies aimed at controlling the modifiable factors may reduce the prevalence of PAD in Asian populations. © The Author(s) 2009.link_to_OA_fulltex
Regional association results for chromosome 19 SNPs in the <i>PVRL2</i>/<i>APOE</i>/<i>TOMM40</i> gene cluster.
<p>The index, associated SNP is named and shown as a purple diamond (rs2075650: <i>P</i> = 1.1×10<sup>−6</sup>).</p
Population characteristics for the individual cohorts.
<p>Population characteristics for the individual cohorts.</p
Comparison of effect sizes for early AMD from this study versus published effect estimates for late AMD.
a<p>Superscript shows reference for the largest study reporting genome-wide association of the relevant SNP with late AMD, from which the “Late AMD” effect estimates were derived:</p>1<p>Chen et al, 2010 <sup>11</sup>.</p>2<p>Yu et al, 2011 <sup>15</sup>.</p>3<p>Klein et al, 2005 <sup>12</sup>.</p>4<p>Kopplin et al, 2010 <sup>13</sup>.</p>5<p>Arakawa et al, 2011 <sup>10</sup>.</p>6<p>Neale et al, 2010 <sup>14</sup>.</p>b<p>NCBI Human Genome Build 36.3 coordinates;</p>c<p>Effective allele;</p>d<p>Frequency of the effective allele;</p>e<p>Summary meta-analysis regression coefficient, indicating the overall, estimated change in log(odds) associated with each additional copy of the effective allele;</p>f<p>Estimated odds ratio and 95% confidence interval for each additional copy of the effective allele, based on fixed-effects meta-analysis of European-ancestry cohorts;</p>g<p><i>P</i>-value associated with the estimated OR;</p>h<p>NR: not reported;</p>i<p><i>P</i>-value from test of heterogeneity of regression coefficients between early and advanced AMD. The threshold for study-wise significance was 0.0036, after accounting for multiple tests. Significant results are shown in bold. Heterogeneity could not be assessed for SNPs with no published confidence interval for the late AMD effect estimate;</p>j<p>Ratio of regression coefficient for advanced vs early AMD, formulated as Beta<sub>adv</sub>/Beta<sub>early</sub>.</p><p><i>Notes:</i> This study did not have data and could not assess association for additional published SNPs rs4711751 in <i>VEGFA</i> and rs11200638 in <i>HTRA1</i>.</p
Comparison of estimated effect sizes for early versus advanced AMD for published SNPs showing genome-wide significant association with AMD.
a<p>Superscript shows reference for the largest study reporting genome-wide association of the relevant SNP with AMD:</p>1<p>Chen et al, 2010 <sup>11</sup>.</p>2<p>Yu et al, 2011 <sup>15</sup>.</p>3<p>Klein et al, 2005 <sup>12</sup>.</p>4<p>Kopplin et al, 2010 <sup>13</sup>.</p>5<p>Arakawa et al, 2011 <sup>10</sup>.</p>6<p>Neale et al, 2010 <sup>14</sup>.</p>b<p>NCBI Human Genome Build 36.3 coordinates;</p>c<p>Effective allele;</p>d<p>Frequency of the effective allele;</p>e<p>Summary meta-analysis regression coefficient, indicating the overall, estimated change in log(odds) associated with each additional copy of the effective allele;</p>f<p>Estimated odds ratio and 95% confidence interval for each additional copy of the effective allele, based on fixed-effects meta-analysis of European-ancestry cohorts;</p>g<p><i>P</i>-value associated with the estimated OR;</p>h<p>Heterogeneity <i>P</i>-value, based on Cochran’s Q statistic;</p>i<p><i>P</i>-value from test of heterogeneity of regression coefficients between early and advanced AMD. The threshold for study-wise significance was 0.0024, after accounting for multiple tests. Significant results are shown in bold;</p>j<p>Ratio of regression coefficient for advanced vs early AMD, formulated as Beta<sub>adv</sub>/Beta<sub>early.</sub></p><p><i>Notes:</i> This study did not have data and could not assess association for additional published SNPs rs4711751 in <i>VEGFA</i> and rs11200638 in <i>HTRA1</i>.</p
Regional association results for chromosome 11 SNPs in the tyrosinase precursor (<i>TYR</i>) gene.
<p>The index, associated SNP is named and shown as a purple diamond (rs621313: <i>P</i> = 3.5×10<sup>−6</sup>).</p
Results for SNPs showing suggestive evidence of association (<i>P</i><1×10<sup>−5</sup>) in the primary (European-ancestry) meta-analysis of early AMD.
<p>Where multiple correlated SNPs in the same gene/region showed similar association evidence, the most strongly associated SNP is shown.</p>a<p>NCBI Human Genome Build 36.3 coordinates;</p>b<p>Effective allele;</p>c<p>Frequency of the effective allele;</p>d<p>Estimated odds ratio and 95% confidence interval for the effect of each additional copy of the effective allele, based on the fixed-effects, inverse variance-weighted meta-analysis of European-ancestry cohorts;</p>e<p><i>P</i>-value associated with the estimated OR;</p>f<p>Heterogeneity <i>I<sup>2</sup></i> statistic;</p>g<p>Heterogeneity <i>P</i>-value, based on Cochran’s Q statistic;</p>h<p>within a 500 kb genomic region centred on the associated SNP.</p