Validating a Genomic Convergence and Network Analysis Approach Using Association Analysis of Identified Candidate Genes in Alzheimer’s Disease

Abstract

Previously, we demonstrated an integrated genomic convergence and network analysis approach to identify the candidate genes associated with the complex neurodegenerative disorder, Alzheimer’s disease (AD). Here, we performed a pilot study to validate the in silico approach by studying the association of genetic variants from three identified critical genes, APOE, EGFR, and ACTB, with AD. A total of 103 patients with AD and 146 healthy controls were recruited. A total of 46 single-nucleotide polymorphisms (SNPs) spanning the three genes were genotyped, of which only 19 SNPs were included in the final analyses after excluding non-polymorphic and Hardy–Weinberg equilibrium-violating SNPs. Apart from our previously reported APOE ε4, four other SNPs in APOE (rs405509, rs7259620, −rs769449, and rs7256173), one in EGFR (rs6970262), and one in ACTB (rs852423) showed a significant association with AD (p < 0.05). Our results validate the reliability of genomic convergence and network analysis approach in identifying the AD-associated candidate genes.

ApoE gene polymorphisms and metals and their interactions with cognitive function

“…The results of the association analysis between genes and cognitive function showed that the rs7412 and rs7259620 alleles of the ApoE gene in codominant and recessive models and the rs405509 allele in the recessive model were associated with cognitive functional status, consistent with the findings of Talwar et al [ 31 ]. The rs429358 allele in this study did not differ significantly between the case and control groups, consistent with the findings of a study of a small population with schizophrenia [ 32 ], but contrary to the findings of Zhen et al, who concluded that the ApoE gene rs429358 was significantly associated with cognitive function in a middle-aged and older male population [ 33 ].…”

ApoE gene polymorphisms and metals and their interactions with cognitive function

“…The results of the association analysis between genes and cognitive function showed that the rs7412 and rs7259620 alleles of the ApoE gene in codominant and recessive models and the rs405509 allele in the recessive model were associated with cognitive functional status, consistent with the ndings of Talwar et al [30] . The rs429358 allele in this study did not differ signi cantly between the case and control groups, consistent with the ndings of a study of a small population with schizophrenia [31] , but contrary to the ndings of Zhen et al, who concluded that the ApoE gene rs429358 was signi cantly associated with cognitive function in a middle-aged and older male population [32] .…”

Leveraging electronic health records and knowledge networks for Alzheimer’s disease prediction and sex-specific biological insights

“…Other genes identified with known associations with AD include APOE , HFE and HSPG2 variants that impact AD risk 49 – 53 . An example of insight gained through SPOKE integration includes ACTB relating to AD 54 , 55 , sensorineural hearing loss 56 , arthropathy and arthritis 57 . The prediction model allows for the prioritization of ACTB for individuals with the common comorbidities of sensorineural hearing loss and arthropathy/arthritis with risk of AD (where the SPOKE informed connection linking sensorineural hearing loss, arthropathy, arthritis and AD all together through ACTB has not been previously implicated in literature).…”