Genetic and regulatory architecture of Alzheimer's disease in the APOE region

Figures

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  Figure 1. Forest plots for the associations of (A) rs429358 (ε4‐coding SNP) and (B) rs7412 (ε2‐coding SNP) with Alzheimer's disease (AD). LOADFS, NIA Late‐Onset Alzheimer's Disease Family Study; HRS, Health and Retirement Study; CHS, Cardiovascular Health Study; FHS_C1, Framingham Heart Study (FHS) original cohort; FHS_C2, FHS offspring cohort; SE, standard error; N, sample size. Meta indicates the results from the meta‐analysis. Horizontal bars show 95% confidence intervals

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  Figure 2. Molecular signature of Alzheimer's disease (AD). Upper‐left triangle: Linkage disequilibrium (LD) pattern (r, %) in the pooled sample from all studies, non‐cases, for 32 single nucleotide polymorphisms (SNPs). Lower‐right triangle: Heat map for Δr = rcases−rnon‐cases representing the molecular signature of AD. Red denotes rcases > rnon‐cases and blue denotes rcases < rnon‐cases. Purple and yellow show the estimates with opposite signs of rcases and rnon‐cases. For convenience, positive sign of rnon‐cases has been selected. Legend on the right shows color‐coded P‐values. The heat map shows that LD changes for the vast majority of SNPs in the entire region spanning all five genes. Numerical estimates are shown in Table S2

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  Figure 3. Significant ε2‐ and ε4‐related molecular signatures of Alzheimer's disease (AD). (A) The ε2‐related signature is characterized by a significant decrease (blue) in linkage disequilibrium (LD) for rs7412 with eight single nucleotide polymorphisms (SNPs) in AD cases compared with non‐cases. (B) The ε4‐related signature is characterized by a significant increase (red) for LD of rs429358 with 13 SNPs, including rs7412, in AD cases compared with non‐cases. Insets show examples of small LD between SNPs indicated by brackets. Vertical lines show 95% confidence intervals. Numerical estimates are shown in Table S2

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  Figure 4. Linkage disequilibrium (LD) patterns in younger and older individuals. Upper‐left triangle: LD pattern (r, %) in younger subjects who were <55 years at biospecimens collection for nine single nucleotide polymorphisms (SNPs) from the TOMM40‐APOE‐APOC1 locus. Lower‐right triangle: Heat map showing Δryo = ryoumg − rold as the difference in LD estimates in younger and older samples. Older sample included subjects with no Alzheimer's disease (AD) who were 55 years and older at biospecimens collection. Numerical estimates are shown in Table S6