Table 2 Functional description and expression of genes associated with the top 30 dataset SNPs in the ADRC dataset
From: Identifying genetic interactions associated with late-onset Alzheimer’s disease
Gene symbol(SNP) | Name | Description | Expression in AD | 1-SNP model rank | p value of pair from PLINK |
|---|---|---|---|---|---|
APOC1 (rs4420638) | Apolipoprotein C-I | Appears to modulate the interaction of APOE with beta-migrating VLDL. Binds free fatty acids. | Overexpressed [38] | 2 | 0.3326 |
TOMM40 (rs157582) | Translocase of outer mitochondrial membrane 40 homolog | Channel-forming subunit of the translocase of the mitochondrial outer membrane (TOM) complex, essential for protein import into mitochondria. | Underexpressed [38] | 3 | 0.4139 |
APOE (rs7412) | Apolipoprotein E | APOE is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. Known risk factor for LOAD. | Overexpressed [38] | 5 | 0.8172 |
SNTG1 (rs16914489) | Gamma-1-syntrophin | Specifically expressed in the brain, highly expressed in the cortex. Organizes the subcellular localization of a variety of proteins. | Overexpressed [38] | 24906 | 0.004546 |
TMEM217 (rs9470543) | Transmembrane protein 217 | Expressed in the brain | - | 4584 | 0.004643 |
SMAD6 (rs3934907) | Mothers against DPP homolog 6 | Negative regulation of BMP and TGF-beta/activin-signaling. BMP-6 is increased in AD brains and leads to impaired neurogenesis [39]. Reduced TGF-beta signaling is involved in neurodegeneration and promotes AD like changes in mice [40]. | Underexpressed [38] | 41282 | 0.0000998 |
NPAS3 (rs4981180) | Neuronal PAS domain protein 3. | Transcription factor. May regulate genes involved in neurogenesis. Associated with schizophrenia and mental retardation | Overexpressed [38] | 1086 | 0.1225 |
NTM (rs11222692) | Neurotrimin | May promote neurite outgrowth and adhesion. NTM lies at locus 11q25, which has been associated with AD [41],[42]. | Overexpressed [38] | 12209 | 0.1422 |
PPAPDC1A (rs4752432) | Phosphatidic acid phosphatase type 2 domain containing 1A | - | - | 6852 | 0.3963 |
NPFF (rs8192593) | Neuropeptide FF-amide peptide precursor | Modulation of morphine-induced antinociception. | - | 3981 | 0.1251 |
SLC25A21 (rs7140725) | Solute carrier family 25 | Known also as ornithine decarboxylase (ODC). Mitochondrial oxoadipate carrier, part of polyamine synthesis pathway. | 444 | 0.06767 | |
RAB23 (rs182662) | Member RAS oncogene family | Intracellular protein transportation. Regulated by miRNA155, which also regulates PICALM (a known AD association). | Underexpressed [38] | 96 | 0.08251 |
UNC5D (rs4577954) | unc-5 homolog D (C. elegans) | Netrin receptor: netrins are secreted proteins that direct axon extension and cell migration during neural development. APP also binds Netrin-1 and in transgenic mice this suppresses amyloid beta peptide production [45]. | - | 63972 | 0.6731 |
CHD9 (rs3852742) | Chromodomain helicase DNA binding protein 9, PPARA -interacting complex 320 kDa protein | Transcriptional co-activator for PPARA. The APOE gene promoter has a binding site for PPAR alpha. Low CHD9 activity could reduce APOE levels. Increase in APOE transcription has been shown to clear amyloid beta in AD mouse models [46]. | Overexpressed [38] | 1061 | 0.04696 |
CNTN4 (rs9819935) | Contactin 4, Brain-derived immunoglobulin superfamily protein 2 | Mainly expressed in brain. Neuronal membrane protein that may play a role in the formation of axon connections in the developing nervous system. Associated with Spinocerebellar Ataxia, Amyotrophic Lateral Sclerosis, 3p deletion syndrome. | - | 2149 | 0.002386 |