Absolute risks for AMD by modeling a general population for various prevalences of AMD (reflecting various age-groups).

1<p>Approximate age-groups corresponding to the modeled prevalences for 65 and 79 years <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037979#pone.0037979-Augood1" target="_blank">[30]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037979#pone.0037979-Friedman1" target="_blank">[31]</a> and for those above 80 years <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037979#pone.0037979-Jonasson1" target="_blank">[32]</a>.</p>2<p>see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037979#pone-0037979-t004" target="_blank">Table 4</a>.</p

Model fit and discriminative accuracy of parsimonious models.

1<p>SNPs from one additional locus at a time were omitted from the 13-SNP model by starting with the locus with the smallest risk.</p>2<p>Numbering corresponds to IDs in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037979#pone-0037979-t002" target="_blank">Table 2</a>.</p>3<p>This model contained the least number of SNPs without compromising R² or AUC values.</p

Risk estimates for each of thirteen AMD risk variants from eight gene loci.

<p>Odds ratios (OR) per risk allele were derived from multiple logistic regression models. Horizontal lines indicate 95% confidence intervals.</p

Area-under-the-curve of the receiver operating characteristic for the 13-SNP genetic risk score and by gene locus.

<p>Observed AUC was 0.820 and the locus-specific AUCs were 0.513, 0.524, 0.536, 0.547, 0.555, 0.571, 0.686 and 0.710 from bottom to top.</p

Five genetic risk groups and relative risk of AMD (ORs and 95% confidence intervals).

1<p>Fraction of individuals in 1000 Genome Project European Ancestry Samples residing in risk groups.</p

Genetic risk score distribution in the study population and in a modeled population.

<p>AMD cases are shown in red, controls in blue, while overlapping bars are shaded blue/red. (<b>A</b>) Genetic risk score distribution for cases (N = 986) and controls (N = 796) in the present study. (<b>B</b>) Counts of cases in (A) were scaled to represent 15% of the total population (assumed as AMD prevalence of the 85–90 year old general population). The density curve represents the risk score distribution in 381 European ancestry samples available through the 1000 Genomes Project (Release 20110521).</p

Two known loci with significant age-difference in genetic effects on late stage AMD.

<p>Shown are the genome-wide significant (P_Agediff < 5 x 10⁻⁸) lead variant at the CFH locus and two of the 34 known variants from Fritsche et al [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0194321#pone.0194321.ref013" target="_blank">13</a>], which revealed significant age-dependency (P_Agediff < 0.05/34, corrected for 34 known lead variants from Fritsche et al). Age-stratified analyses included 17,031 younger (7,959 cases, 9,072 controls) and 16,587 older (7,934 cases, 8,653 controls) individuals.</p

LD region plots of two AMD loci with genome-wide significant joint 2df age-stratified P-Values that were undetected by Fritsche et al.

<p>Shown are the age-joint P-Values (P_Agejoint) for late AMD by their position on chromosome 15 and chromosome 18. The figures were created using Locuszoom (<b><a href="http://locuszoom.sph.umich.edu/" target="_blank">http://locuszoom.sph.umich.edu/</a></b>).</p

Gene prioritization scoring for two AMD regions that were undetected by Fritsche et al.

<p>We queried 11 genes in the 2 narrow AMD regions (index and proxies, r² ≥ 0.5 and ±500 kb) for biological evidence. Detailed results are shown in the supplement for the expression data (<b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0194321#pone.0194321.s005" target="_blank">S5 Table</a></b>) and the functional annotation (<b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0194321#pone.0194321.s004" target="_blank">S4 Table</a></b>) as well as for the mouse data (<b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0194321#pone.0194321.s006" target="_blank">S6 Table</a></b>).</p

Manhattan and QQ plot of age-difference P-values.

<p>Shown are the age-difference P-Values for late AMD by their position on the genome (A, Manhattan plot) as well as their distribution (B, QQ plot). The 34 known genetic regions identified by Fritsche et al [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0194321#pone.0194321.ref013" target="_blank">13</a>] are colored blue in the Manhattan plot.</p