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

Jin Li, Qiushi Zhang, Feng Chen, Jingwen Yan, Sungeun Kim, Lei Wang, Weixing Feng, Andrew Saykin, Hong Liang, Li Shen

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number647389
JournalBioMed Research International
Volume2015
DOIs
StatePublished - 2015

Fingerprint

Genome-Wide Association Study
Amyloid
Genes
Alzheimer Disease
Single Nucleotide Polymorphism
Association reactions
Genome
Phenotype
Neuroimaging
Neurodegenerative Diseases
Biomarkers
Statistics
Imaging techniques

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Genetic Interactions Explain Variance in Cingulate Amyloid Burden : An AV-45 PET Genome-Wide Association and Interaction Study in the ADNI Cohort. / Li, Jin; Zhang, Qiushi; Chen, Feng; Yan, Jingwen; Kim, Sungeun; Wang, Lei; Feng, Weixing; Saykin, Andrew; Liang, Hong; Shen, Li.

In: BioMed Research International, Vol. 2015, 647389, 2015.

Research output: Contribution to journalArticle

Li, Jin ; Zhang, Qiushi ; Chen, Feng ; Yan, Jingwen ; Kim, Sungeun ; Wang, Lei ; Feng, Weixing ; Saykin, Andrew ; Liang, Hong ; Shen, Li. / Genetic Interactions Explain Variance in Cingulate Amyloid Burden : An AV-45 PET Genome-Wide Association and Interaction Study in the ADNI Cohort. In: BioMed Research International. 2015 ; Vol. 2015.
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