Structural Neuroimaging Genetics Interactions in Alzheimer's Disease.

TitleStructural Neuroimaging Genetics Interactions in Alzheimer's Disease.
Publication TypeJournal Article
Year of Publication2015
AuthorsMoon, Seok Woo, Dinov Ivo D., Kim Jaebum, Zamanyan Alen, Hobel Sam, Thompson Paul M., and Toga Arthur W.
JournalJ Alzheimers Dis
Volume48
Issue4
Pagination1051-63
Date Published2015
ISSN1875-8908
KeywordsAged, Alzheimer Disease, Apolipoproteins E, Brain, Cognitive Dysfunction, Female, Follow-Up Studies, Genetic Association Studies, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Polymorphism, Single Nucleotide, Prospective Studies, Software
Abstract

This article investigates late-onset cognitive impairment using neuroimaging and genetics biomarkers for Alzheimer's Disease Neuroimaging Initiative (ADNI) participants. Eight-hundred and eight ADNI subjects were identified and divided into three groups: 200 subjects with Alzheimer's disease (AD), 383 subjects with mild cognitive impairment (MCI), and 225 asymptomatic normal controls (NC). Their structural magnetic resonance imaging (MRI) data were parcellated using BrainParser, and the 80 most important neuroimaging biomarkers were extracted using the global shape analysis Pipeline workflow. Using Plink via the Pipeline environment, we obtained 80 SNPs highly-associated with the imaging biomarkers. In the AD cohort, rs2137962 was significantly associated bilaterally with changes in the hippocampi and the parahippocampal gyri, and rs1498853, rs288503, and rs288496 were associated with the left and right hippocampi, the right parahippocampal gyrus, and the left inferior temporal gyrus. In the MCI cohort, rs17028008 and rs17027976 were significantly associated with the right caudate and right fusiform gyrus, rs2075650 (TOMM40) was associated with the right caudate, and rs1334496 and rs4829605 were significantly associated with the right inferior temporal gyrus. In the NC cohort, Chromosome 15 [rs734854 (STOML1), rs11072463 (PML), rs4886844 (PML), and rs1052242 (PML)] was significantly associated with both hippocampi and both insular cortices, and rs4899412 (RGS6) was significantly associated with the caudate. We observed significant correlations between genetic and neuroimaging phenotypes in the 808 ADNI subjects. These results suggest that differences between AD, MCI, and NC cohorts may be examined by using powerful joint models of morphometric, imaging and genotypic data.

DOI10.3233/JAD-150335
Alternate JournalJ. Alzheimers Dis.
PubMed ID26444770
PubMed Central IDPMC4730943
Grant ListK01 AG030514 / AG / NIA NIH HHS / United States
P41 EB015922 / EB / NIBIB NIH HHS / United States
P50 AG16570 / AG / NIA NIH HHS / United States
U54 EB020406 / EB / NIBIB NIH HHS / United States
R21 RR019771 / RR / NCRR NIH HHS / United States
R01 LM005639 / LM / NLM NIH HHS / United States
U01 AG024904 / AG / NIA NIH HHS / United States
EB01651 / EB / NIBIB NIH HHS / United States
P20 NR015331 / NR / NINR NIH HHS / United States
2-P41-RR-013642-15 / RR / NCRR NIH HHS / United States
P30 DK089503 / DK / NIDDK NIH HHS / United States
U24-RR021992 / RR / NCRR NIH HHS / United States
RR019771 / RR / NCRR NIH HHS / United States
9P41EB015922-15 / EB / NIBIB NIH HHS / United States
P41 RR013642 / RR / NCRR NIH HHS / United States
U54 RR021813 / RR / NCRR NIH HHS / United States
U24 RR021992 / RR / NCRR NIH HHS / United States
LM05639 / LM / NLM NIH HHS / United States
P50 NS091856 / NS / NINDS NIH HHS / United States
P30 AG010129 / AG / NIA NIH HHS / United States
R01 MH071940 / MH / NIMH NIH HHS / United States
U24 RR025736 / RR / NCRR NIH HHS / United States
U24-RR025736 / RR / NCRR NIH HHS / United States