Association of common and rare variants with Alzheimer's disease in more than 13,000 diverse individuals with whole-genome sequencing from the Alzheimer's Disease Sequencing Project.

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dc.citation.volumeEarly View
dc.contributor.authorLee W-P
dc.contributor.authorChoi SH
dc.contributor.authorShea MG
dc.contributor.authorCheng P-L
dc.contributor.authorDombroski BA
dc.contributor.authorPitsillides AN
dc.contributor.authorHeard-Costa NL
dc.contributor.authorWang H
dc.contributor.authorBulekova K
dc.contributor.authorKuzma AB
dc.contributor.authorLeung YY
dc.contributor.authorFarrell JJ
dc.contributor.authorLin H
dc.contributor.authorKunkle BW
dc.contributor.authorNaj A
dc.contributor.authorBlue EE
dc.contributor.authorNusetor F
dc.contributor.authorWang D
dc.contributor.authorBoerwinkle E
dc.contributor.authorBush WS
dc.contributor.authorZhang X
dc.contributor.authorDe Jager PL
dc.contributor.authorDupuis J
dc.contributor.authorFarrer LA
dc.contributor.authorFornage M
dc.contributor.authorMartin E
dc.contributor.authorPericak-Vance M
dc.contributor.authorSeshadri S
dc.contributor.authorWijsman EM
dc.contributor.authorWang L-S
dc.contributor.authorAlzheimer's Disease Sequencing Project
dc.contributor.authorSchellenberg GD
dc.contributor.authorDestefano AL
dc.contributor.authorHaines JL
dc.contributor.authorPeloso GM
dc.coverage.spatialUnited States
dc.date.accessioned2024-12-11T20:39:24Z
dc.date.available2024-12-11T20:39:24Z
dc.date.issued2024-10-20
dc.description.abstractINTRODUCTION Alzheimer's disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous. METHODS We investigated the association of AD with both common variants and aggregates of rare coding and non-coding variants in 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data. RESULTS Pooled-population analyses of all individuals identified genetic variants at apolipoprotein E (APOE) and BIN1 associated with AD (p < 5 × 10−8). Subgroup-specific analyses identified a haplotype on chromosome 14 including PSEN1 associated with AD in Hispanics, further supported by aggregate testing of rare coding and non-coding variants in the region. Common variants in LINC00320 were observed associated with AD in Black individuals (p = 1.9 × 10−9). Finally, we observed rare non-coding variants in the promoter of TOMM40 distinct of APOE in pooled-population analyses (p = 7.2 × 10−8). DISCUSSION We observed that complementary pooled-population and subgroup-specific analyses offered unique insights into the genetic architecture of AD. Highlights We determine the association of genetic variants with Alzheimer's disease (AD) using 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data. We identified genetic variants at apolipoprotein E (APOE), BIN1, PSEN1, and LINC00320 associated with AD. We observed rare non-coding variants in the promoter of TOMM40 distinct of APOE.
dc.description.confidentialfalse
dc.identifier.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/39428839
dc.identifier.citationLee W-P, Choi SH, Shea MG, Cheng P-L, Dombroski BA, Pitsillides AN, Heard-Costa NL, Wang H, Bulekova K, Kuzma AB, Leung YY, Farrell JJ, Lin H, Kunkle BW, Naj A, Blue EE, Nusetor F, Wang D, Boerwinkle E, Bush WS, Zhang X, De Jager PL, Dupuis J, Farrer LA, Fornage M, Martin E, Pericak-Vance M, Seshadri S, Wijsman EM, Wang L-S, Alzheimer's Disease Sequencing Project , Schellenberg GD, Destefano AL, Haines JL, Peloso GM. (2024). Association of common and rare variants with Alzheimer's disease in more than 13,000 diverse individuals with whole-genome sequencing from the Alzheimer's Disease Sequencing Project.. Alzheimers Dement. Early View.
dc.identifier.doi10.1002/alz.14283
dc.identifier.eissn1552-5279
dc.identifier.elements-typejournal-article
dc.identifier.issn1552-5260
dc.identifier.urihttps://mro.massey.ac.nz/handle/10179/72273
dc.languageeng
dc.publisherWiley Periodicals LLC on behalf of Alzheimer's Association
dc.publisher.urihttps://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.14283
dc.relation.isPartOfAlzheimers Dement
dc.rights(c) 2024 The Author/s
dc.rightsCC BY-NC-ND 4.0
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAlzheimer's disease
dc.subjectgenetics
dc.subjectrare genetic variants
dc.subjectwhole genome sequencing
dc.titleAssociation of common and rare variants with Alzheimer's disease in more than 13,000 diverse individuals with whole-genome sequencing from the Alzheimer's Disease Sequencing Project.
dc.typeJournal article
pubs.elements-id492036
pubs.organisational-groupCollege of Health
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