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> = 1.1×10⁻⁶).</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 ¹¹.</p>2<p>Yu et al, 2011 ¹⁵.</p>3<p>Klein et al, 2005 ¹².</p>4<p>Kopplin et al, 2010 ¹³.</p>5<p>Arakawa et al, 2011 ¹⁰.</p>6<p>Neale et al, 2010 ¹⁴.</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_adv/Beta_early.</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

Population characteristics for the individual cohorts.

<p>Population characteristics for the individual cohorts.</p

Results for SNPs showing suggestive evidence of association (<i>P</i>&lt;1×10⁻⁵) 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>I²</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

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 ¹¹.</p>2<p>Yu et al, 2011 ¹⁵.</p>3<p>Klein et al, 2005 ¹².</p>4<p>Kopplin et al, 2010 ¹³.</p>5<p>Arakawa et al, 2011 ¹⁰.</p>6<p>Neale et al, 2010 ¹⁴.</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_adv/Beta_early.</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> = 3.5×10⁻⁶).</p

Quantitative trait analysis between <i>ABCC5</i> rs1401999 and anterior chamber depth in SIMES, SINDI, and BES.

<p>SIMES: Singapore Malay Eye Study (typed with Illumina 610K GWAS chip).</p><p>SINDI: Singapore Indian Eye Study (typed with Illumina 610K GWAS chip).</p><p>BES1: Beijing Eye Study typed with Illumina 610K GWAS chip.</p><p>BES2: Beijing Eye Study typed with direct sequencing.</p><p>β: Per-allele effect size of <i>ABCC5</i> rs1401999 on anterior chamber depth.</p><p>SE: Standard error for β.</p><p><i>P</i>gc: Genomic control corrected <i>P</i>-value.</p><p>MAF: Minor allele frequency.</p><p>*: I²-index for heterogeneity = 0%.</p

Association analysis between <i>ABCC5</i> rs1401999 and primary angle closure glaucoma in all chip-typed sample collections (top panel), de-novo genotyped sample collections (middle panel), and PACG cases and clinically certified controls with open angles (bottom panel).

<p>MAF case: Minor allele frequency in PACG cases.</p><p>MAF control: Minor allele frequency in controls.</p><p>OR: Odds ratio.</p><p><i>P</i>: <i>P</i>-value for association with PACG.</p><p>I²: I-squared index for between-collection heterogeneity.</p><p>* Results here are presented based on raw minor allele frequency counts without further adjustment.</p>†<p>PACG patients were recruited from the Beijing Tongren Hospital and controls were recruited from the Handan Eye Study (HES), a population-based study of eye disease in rural Chinese aged 30 years and over.</p

Association analysis between <i>ABCC5</i> rs1401999 and susceptibility to primary angle closure glaucoma (PACG).

<p>The PACG sample collections have been described elsewhere <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004089#pgen.1004089-Vithana1" target="_blank">[6]</a>. The vertical line represents a per-allele odds ratio of 1.00. The oblongs represent point estimates (referring to the per-allele odds ratio), with the height of the oblongs inversely proportional to the standard error of the point estimates. Horizontal lines indicate the 95% confidence interval for each point estimate. Meta-analyses of samples are reflected by blue diamonds. The width of the diamonds indicates their 95% confidence intervals. All point estimates in Stage 1 have been adjusted for the top axes of genetic stratification using logistic regression.</p