title: Genetic Interactions Explain Variance in Cingulate Amyloid Burden: An AV-45 PET Genome-Wide Association and Interaction Study in the ADNI Cohort.
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.
authors.affiliation: Institute of Biomedical Engineering, College of Automation, Harbin Engineering University, 145 Nantong Street, Harbin 150001, China ; Center for Bioinformatics, College of Automation, Harbin Engineering University, 145 Nantong Street, Harbin 150001, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Biomedical Engineering, College of Automation, Harbin Engineering University, 145 Nantong Street, Harbin 150001, China ; Center for Bioinformatics, College of Automation, Harbin Engineering University, 145 Nantong Street, Harbin 150001, China ; College of Information Engineering, Northeast Dianli University, 169 Changchun Street, Jilin 132012, China.
authors.forename: Qiushi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Institute of Biomedical Engineering, College of Automation, Harbin Engineering University, 145 Nantong Street, Harbin 150001, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 355 West 16th Street, Suite 4100, Indianapolis, IN 46202, USA ; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, 410 West 10th Street, Suite 5000, Indianapolis, IN 46202, USA ; Department of Biohealth Informatics, Indiana University School of Informatics and Computing, Indianapolis, IN 46202, USA.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Yan
authors.affiliation: Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 355 West 16th Street, Suite 4100, Indianapolis, IN 46202, USA.
authors.forename: Sungeun
authors.initials: S
authors.lastname: Kim
authors.affiliation: Institute of Biomedical Engineering, College of Automation, Harbin Engineering University, 145 Nantong Street, Harbin 150001, China ; Center for Bioinformatics, College of Automation, Harbin Engineering University, 145 Nantong Street, Harbin 150001, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Biomedical Engineering, College of Automation, Harbin Engineering University, 145 Nantong Street, Harbin 150001, China ; Center for Bioinformatics, College of Automation, Harbin Engineering University, 145 Nantong Street, Harbin 150001, China.
authors.forename: Weixing
authors.initials: W
authors.lastname: Feng
authors.affiliation: Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 355 West 16th Street, Suite 4100, Indianapolis, IN 46202, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Saykin
authors.affiliation: Institute of Biomedical Engineering, College of Automation, Harbin Engineering University, 145 Nantong Street, Harbin 150001, China ; Center for Bioinformatics, College of Automation, Harbin Engineering University, 145 Nantong Street, Harbin 150001, China ; Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 355 West 16th Street, Suite 4100, Indianapolis, IN 46202, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Liang
authors.affiliation: Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 355 West 16th Street, Suite 4100, Indianapolis, IN 46202, USA ; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, 410 West 10th Street, Suite 5000, Indianapolis, IN 46202, USA ; Department of Biohealth Informatics, Indiana University School of Informatics and Computing, Indianapolis, IN 46202, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Shen
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D000682:Amyloid / Q000378:metabolism*; D015331:Cohort Studies; D004843:Epistasis, Genetic; D005260:Female; D055106:Genome-Wide Association Study; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D059906:Neuroimaging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D049268:Positron-Emission Tomography
chemical_list: D000682:Amyloid