Table 1.
Characteristics of HRS participants at the first assessment point, tested for immediate and delayed recall between 1996 and 2012, in the HRS full and Non-Hispanic White (NHW) genotypic samples.
Fig 1.
Scores (as words recalled) for immediate, delayed, and residualized delayed recall among 20,650 participants in the HRS.
Table 2.
Age-adjusted values for estimated immediate recall (IR), delayed recall (DR), and residual delayed recall (rDR) in HRS.
Fig 2.
P-values for all 1,198,956 SNP associations from GWAS on the HRS genetic sample.
(A) Level of Immediate Recall (IR-L); (B) Change in Immediate Recall (IR-C); (C) Level of Residualized Delayed Recall (rDR-L); (D) Change in Residualized Delayed Recall (rDR-C). For these figures, the upper (red) horizontal line demarcates the threshold of p = -log(5.0x10-08) and the lower (blue) horizontal line demarcates p = -log(1x10-05). SNPs are arranged by their chromosomal position (x-axis).
Table 3.
Strongest associated SNPs detected by GWASs in the HRS discovery sample and comparisons in the ELSA replication sample, for immediate recall level (IR-L) and change (IR-C) and residual delayed recall level (rDR-L) and change (rDR-C).
Fig 3.
Regional plot showing the results for the association between rDR-L in HRS, with the top SNP in TOMM40 (rs2075650) identified.
The y-axis shows -log10 P-values; x-axis shows position of genes on chromosome 19. The diamond (purple) represents the top genome-wide significant SNP. The circles represent each genotyped SNP in the region 400-kb in both directions from rs2075650; the circle color indicates pairwise linkage disequilibrium (LD) in relation to the top SNP (calculated from hg19/1000 Genomes Nov 2014 EUR). The solid (blue) line indicates the recombination rate.
Table 4.
Meta-analyses results for SNPs reaching genome-wide significance for all four phenotypes: Immediate recall level (IR-L), immediate recall change (IR-C), residualized delayed recall level (rDR-L), and residualized delayed recall change (rDR-C).
Fig 4.
Regional plots showing meta-analyses results for rDR-L.
(A) Results with the top associated SNP in the APOE region labeled. Two conditional meta-analyses were performed for rDR-L, (B) estimating the association with the APOE SNP shown (rs769449), conditioning on the top TOMM40 SNP (rs2075650); and (C) estimating the association with the TOMM40 SNP shown (rs2075650), conditioning on the top APOE SNP (rs769449). The y-axis shows -log10 P-values; x-axis shows position of genes on chromosome 19 with SNPs 400-kb in both directions of the SNP of interest. The diamond represents the top SNP of interest. The circles represent each genotyped SNP in this region; the circle color indicates pairwise linkage disequilibrium (LD) in relation to the top SNP (calculated from hg19/1000 Genomes Nov 2014 EUR). The solid (blue) line indicates the recombination rate.
Fig 5.
Regional plots showing results of the meta-analyses of IR-C.
(A) Meta-analysis results with the top SNP in TOMM40 (rs157582) shown; (B) results when estimating the association with the TOMM40 SNP shown (rs157582), conditioning on the top APOE SNP (rs769449); and (C) results when estimating the association with the APOE SNP (rs769449), conditioning on the top TOMM40 SNP (rs157582). The y-axis shows -log10 P-values; x-axis shows position of genes on chromosome 19 with SNPs 400-kb in both directions of the SNP of interest. The diamond represents the top SNP of interest. The circles represent each genotyped SNP in this region; the circle color indicates pairwise linkage disequilibrium (LD) in relation to the top SNP (calculated from hg19/1000 Genomes Nov 2014 EUR). The solid (blue) line indicates the recombination rate.
Fig 6.
Plot of effect sizes of top TOMM40 risk alleles against age, adjusted for APOE e4 presence.
(A) Effect of the G allele in rs2075650 on rDR-L and (B) Effect of the A allele in rs157582 on IR-C. The lines represent age-related trajectories of the phenotype for individuals who have no risk alleles (solid line) or 1 or more risk allele (dashed line).