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Genetic associations of in vivo pathology influence Alzheimers disease susceptibility

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dc.contributor.authorSeo, Jieun-
dc.contributor.authorByun, Min Soo-
dc.contributor.authorYi, Dahyun-
dc.contributor.authorLee, Jun Ho-
dc.contributor.authorJeon, So Yeon-
dc.contributor.authorShin, Seong A-
dc.contributor.authorKim, Yu Kyeong-
dc.contributor.authorKang, Koung Mi-
dc.contributor.authorSohn, Chul-Ho-
dc.contributor.authorJung, Gijung-
dc.contributor.authorPark, Jong-Chan-
dc.contributor.authorHan, Sun-Ho-
dc.contributor.authorByun, Jayoung-
dc.contributor.authorMook-Jung, Inhee-
dc.contributor.authorLee, Dong Young-
dc.contributor.authorChoi, Murim-
dc.date.accessioned2021-01-27T06:06:25Z-
dc.date.available2021-01-27T15:08:38Z-
dc.date.issued2020-11-19-
dc.identifier.citationAlzheimer's Research & Therapy. 2020 Nov 19;12(1):156ko_KR
dc.identifier.issn1758-9193-
dc.identifier.urihttps://hdl.handle.net/10371/171713-
dc.description.abstractIntroduction
Although the heritability of sporadic Alzheimers disease (AD) is estimated to be 60–80%, addressing the genetic contribution to AD risk still remains elusive. More specifically, it remains unclear whether genetic variants are able to affect neurodegenerative brain features that can be addressed by in vivo imaging techniques.

Methods
Targeted sequencing analysis of the coding and UTR regions of 132 AD susceptibility genes was performed. Neuroimaging data using 11C-Pittsburgh Compound B positron emission tomography (PET), 18F-fluorodeoxyglucose PET, and MRI that are available from the KBASE (Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimers disease) cohort were acquired. A total of 557 participants consisted of 336 cognitively normal (CN) adults, 137 mild cognitive impairment (MCI), and 84 AD dementia (ADD) groups.

Results
We called 5391 high-quality single nucleotide variants (SNVs) on AD susceptibility genes and selected significant associations between variants and five in vivo AD pathologies: (1) amyloid β (Aβ) deposition, (2) AD-signature region cerebral glucose metabolism (AD-Cm), (3) posterior cingulate cortex (PCC) cerebral glucose metabolism (PCC-Cm), (4) AD-signature region cortical thickness (AD-Ct), and (5) hippocampal volume (Hv). The association analysis for common variants (allele frequency (AF) > 0.05) yielded several novel loci associated with Aβ deposition (PIWIL1-rs10848087), AD-Cm (NME8-rs2722372 and PSEN2-rs75733498), AD-Ct (PSEN1-rs7523) and, Hv (CASS4-rs3746625). Meanwhile, in a gene-based analysis for rare variants (AF < 0.05), cases carrying rare variants in LPL, FERMT2, NFAT5, DSG2, and ITPR1 displayed associations with the neuroimaging features. Exploratory voxel-based brain morphometry between the variant carriers and non-carriers was performed subsequently. Finally, we document a strong association of previously reported APOE variants with the in vivo AD pathologies and demonstrate that the variants exert a causal effect on AD susceptibility via neuroimaging features.

Conclusions
This study provides novel associations of genetic factors to Aβ accumulation and AD-related neurodegeneration to influence AD susceptibility.
ko_KR
dc.description.sponsorshipThe study was supported by grants from the National Research Foundation of Korea (2014M3C7A1046049 and 2018M3C9A5064708 for Choi M and 2014M3C7A1046042 for Lee DY) and grants from the Ministry of Health and Welfare of Korea (HI18C0630 for Mook-Jung IH and Lee DY, and HI19C0149 for Lee DY).ko_KR
dc.language.isoenko_KR
dc.publisherBMCko_KR
dc.subjectAlzheimer’s disease-
dc.subjectTargeted panel sequencing-
dc.subjectGenetic association-
dc.subjectNeuroimaging-
dc.subjectIn vivo AD pathologies-
dc.subjectPET-
dc.subjectMRI-
dc.titleGenetic associations of in vivo pathology influence Alzheimers disease susceptibilityko_KR
dc.typeArticleko_KR
dc.contributor.AlternativeAuthor서지은-
dc.contributor.AlternativeAuthor변민수-
dc.contributor.AlternativeAuthor이다현-
dc.contributor.AlternativeAuthor이준호-
dc.contributor.AlternativeAuthor전소연-
dc.contributor.AlternativeAuthor신성아-
dc.contributor.AlternativeAuthor김유경-
dc.contributor.AlternativeAuthor강경미-
dc.contributor.AlternativeAuthor손철호-
dc.contributor.AlternativeAuthor박종찬-
dc.contributor.AlternativeAuthor한선호-
dc.contributor.AlternativeAuthor변자영-
dc.contributor.AlternativeAuthor이동영-
dc.contributor.AlternativeAuthor최무림-
dc.identifier.doi10.1186/s13195-020-00722-2-
dc.citation.journaltitleAlzheimer's Research & Therapyko_KR
dc.language.rfc3066en-
dc.rights.holderThe Author(s)-
dc.date.updated2020-11-22T04:31:41Z-
dc.citation.number1ko_KR
dc.citation.startpage156ko_KR
dc.citation.volume12ko_KR
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biomedical Sciences (대학원 의과학과)Journal Papers (저널논문_의과학과)
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