Testing for the influence of single genetic variants on age-specific mortality in the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort.

<p>(A) Manhattan plot of <i>P</i> values for the change in allele frequency with age. The red line marks the <i>P</i> = 5 × 10⁻⁸ threshold. (B) Allele frequency trajectory of rs6857, a tag SNP for the <i>APOE ε</i>4 allele, with age. Data points are the frequencies of the risk allele within 5-year interval age bins (± 2 SE), with the center of the bin indicated on the x-axis (except for the first and the last points). Bins with ages below 38 years are merged into 1 bin because of the relatively small sample sizes. The dashed line shows the expected frequency based on the null model, accounting for confounding batch effects and changes in ancestry (see <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2002458#sec007" target="_blank">Materials and methods</a>). In orange are the mean ages at onset of Alzheimer disease for carriers of 0, 1, or 2 copies of the <i>APOE ε</i>4 allele [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2002458#pbio.2002458.ref053" target="_blank">53</a>]. See <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2002458#pbio.2002458.s035" target="_blank">S1 Data</a> for underlying data.