Table 3.
Biological roles of top SNPs (and genes) that showed significant associations with AD in more than one dataset (CHS, FHS, HRS or LOADFS) using logistic and/or Cox model.
| SNP | Closest gene (involved in, associated with) | LD with (0.4 ≤ r2; D′ > 0.7) | eQTL (SNP influences expression of) | SNP is in enhancer region in | SNP was previously associated with | References |
|---|---|---|---|---|---|---|
| rs2075650 | TOMM40 (protein precursors’ import into mitochondria, AD)a | rs429358 and rs769449 in APOE; SNPs in PVRL2 | TOMM40, PVRL2 | 12 tissues | Longevity, AD; LDLC | (Harold et al., 2009; Deelen et al., 2011; Holliday et al., 2013; Abe et al., 2015) |
| rs405509 | APOE (lipid transport, AD, stroke, cancer, longevity, hippocampus atrophy, response to viruses (HCV))b | SNPs in TOMM40; PVRL2 | APOE, PVRL2 | 10 tissues | Longevity, AD; cognitive impairment (interacts with APOE e4) | (Wang et al., 2017; Lu et al., 2014; Ryu et al., 2016; Ma et al., 2016) |
| rs8106922 | TOMM40 (protein precursors’ import into mitochondria, AD) | SNPs in APOE; PVRL2 | PVRL2 | blood | Longevity; TG | (Lin et al., 2016; Salakhov et al., 2014) |
| rs6859 | PVRL2 (adherens junctions, resistance to herpesviruses, cancer prognosis) | SNPs in PVRL2 | PVRL2, TOMM40 | 7 tissues | AD | (Logue et al., 2011) |
| rs12721046 | APOC1 (AD, cancer, HDL, VLDL, virus (HCV) infectivity) | rs769449 and rs429358 in APOE | LDL, HDL | (Kettunen et al., 2012; Musunuru et al., 2012) | ||
| rs769449 | APOE (lipid transport, AD, stroke, cancer, longevity, response to viruses (HCV)) | rs429358 in APOE, rs12721046 in APOC1, rs2075650 in TOMM40; SNPs in PVRL2 | 5 tissues | CSF tau levels, cognitive decline, LDL | (Cruchaga et al., 2013; Zhang and Pierce, 2014; Kettunen et al., 2012) |
a
Biological effects of SNPs were assessed using NCBI resources (PubMed, dbSNP, etc.), NHGRI-EBI Catalog of published GWAS (https://www.ebi.ac.uk/gwas), GRASP (https://grasp.nhlbi.nih.gov), and HaploReg v4.1 (Ward and Kellis, 2016) (http://archive.broadinstitute.org/mammals/haploreg).
b
LD with other genes column also shows LD with rs429358, one of two SNP defining APOE e2/e3/e4 polymorphism, and LD between individual SNPs shown in the table.