Genetic Interactions Explain Variance in Cingulate Amyloid Burden: An AV-45 PET Genome-Wide Association and Interaction Study in the ADNI Cohort

Alzheimer’s disease (AD) is the most common neurodegenerative disorder. Using discrete disease status as the phenotype and computing statistics at the single marker level may not be able to address the underlying biological interactions that contribute to disease mechanism and may contribute to the...

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Veröffentlicht in:BioMed research international 2015-01, Vol.2015 (2015), p.1-11
Hauptverfasser: Shen, Li, Liang, Hong, Feng, Weixing, Wang, Lei, Kim, Sungeun, Yan, Jingwen, Chen, Feng, Zhang, Qiushi, Li, Jin, Saykin, Andrew J.
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Sprache:eng
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Zusammenfassung:Alzheimer’s disease (AD) is the most common neurodegenerative disorder. Using discrete disease status as the phenotype and computing statistics at the single marker level may not be able to address the underlying biological interactions that contribute to disease mechanism and may contribute to the issue of “missing heritability.” We performed a genome-wide association study (GWAS) and a genome-wide interaction study (GWIS) of an amyloid imaging phenotype, using the data from Alzheimer’s Disease Neuroimaging Initiative. We investigated the genetic main effects and interaction effects on cingulate amyloid-beta (Aβ) load in an effort to better understand the genetic etiology of Aβ deposition that is a widely studied AD biomarker. PLINK was used in the single marker GWAS, and INTERSNP was used to perform the two-marker GWIS, focusing only on SNPs with p≤0.01 for the GWAS analysis. Age, sex, and diagnosis were used as covariates in both analyses. Corrected p values using the Bonferroni method were reported. The GWAS analysis revealed significant hits within or proximal to APOE, APOC1, and TOMM40 genes, which were previously implicated in AD. The GWIS analysis yielded 8 novel SNP-SNP interaction findings that warrant replication and further investigation.
ISSN:2314-6133
2314-6141
DOI:10.1155/2015/647389