You are here

Translating Alzheimer's disease-associated polymorphisms into functional candidates: a survey of IGAP genes and SNPs.

TitleTranslating Alzheimer's disease-associated polymorphisms into functional candidates: a survey of IGAP genes and SNPs.
Publication TypeJournal Article
Year of Publication2019
AuthorsKatsumata Y, Nelson PT, Estus S, Fardo DW
Corporate AuthorsAlzheimer's Disease Neuroimaging Initiative(ADNI)
JournalNeurobiol Aging
Volume74
Pagination135-146
Date Published2019 02
ISSN1558-1497
KeywordsAged, Aged, 80 and over, Alzheimer Disease, Carrier Proteins, CELF1 Protein, Desmoglein 2, Female, Genetic Association Studies, Humans, Linkage Disequilibrium, Male, Membrane Proteins, Polymorphism, Single Nucleotide, Quantitative Trait Loci, RNA, Messenger, RNA, Untranslated, SAP90-PSD95 Associated Proteins, Transcription, Genetic
Abstract

The International Genomics of Alzheimer's Project (IGAP) is a consortium for characterizing the genetic landscape of Alzheimer's disease (AD). The identified and/or confirmed 19 single-nucleotide polymorphisms (SNPs) associated with AD are located on non-coding DNA regions, and their functional impacts on AD are as yet poorly understood. We evaluated the roles of the IGAP SNPs by integrating data from many resources, based on whether the IGAP SNP was (1) a proxy for a coding SNP or (2) associated with altered mRNA transcript levels. For (1), we confirmed that 12 AD-associated coding common SNPs and five nonsynonymous rare variants are in linkage disequilibrium with the IGAP SNPs. For (2), the IGAP SNPs in CELF1 and MS4A6A were associated with expression of their neighboring genes, MYBPC3 and MS4A6A, respectively, in blood. The IGAP SNP in DSG2 was an expression quantitative trait loci (eQTL) for DLGAP1 and NETO1 in the human frontal cortex. The IGAP SNPs in ABCA7, CD2AP, and CD33 each acted as eQTL for AD-associated genes in brain. Our approach for identifying proxies and examining eQTL highlighted potentially impactful, novel gene regulatory phenomena pertinent to the AD phenotype.

DOI10.1016/j.neurobiolaging.2018.10.017
Pubmed Linkhttps://www.ncbi.nlm.nih.gov/pubmed/30448613?dopt=Abstract
page_expoExternal
Alternate JournalNeurobiol. Aging
PubMed ID30448613
PubMed Central IDPMC6331247
Grant ListR01 AG015819 / AG / NIA NIH HHS / United States
P30 AG013854 / AG / NIA NIH HHS / United States
UL1 TR000117 / TR / NCATS NIH HHS / United States
HHSN268201100012C / HL / NHLBI NIH HHS / United States
P50 MH060451 / MH / NIMH NIH HHS / United States
ZIA AG000932 / ImNIH / Intramural NIH HHS / United States
RC2 HL102419 / HL / NHLBI NIH HHS / United States
UL1 TR001445 / TR / NCATS NIH HHS / United States
R01 AG054060 / AG / NIA NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
R01 AG022374 / AG / NIA NIH HHS / United States
P30 AG010124 / AG / NIA NIH HHS / United States
P50 AG023501 / AG / NIA NIH HHS / United States
U01 HG006375 / HG / NHGRI NIH HHS / United States
U01 HL096812 / HL / NHLBI NIH HHS / United States
K25 AG043546 / AG / NIA NIH HHS / United States
U54 AG052427 / AG / NIA NIH HHS / United States
R01 NS017950 / NS / NINDS NIH HHS / United States
RC2 AG036528 / AG / NIA NIH HHS / United States
P30 AG028377 / AG / NIA NIH HHS / United States
P50 AG008671 / AG / NIA NIH HHS / United States
R01 AG054076 / AG / NIA NIH HHS / United States
P50 AG005142 / AG / NIA NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
R01 AG035137 / AG / NIA NIH HHS / United States
G1100540 / MRC_ / Medical Research Council / United Kingdom
U54 HG003067 / HG / NHGRI NIH HHS / United States
P50 AG005131 / AG / NIA NIH HHS / United States
R01 AG015928 / AG / NIA NIH HHS / United States
P50 AG005128 / AG / NIA NIH HHS / United States
P30 AG010133 / AG / NIA NIH HHS / United States
U24 AG021886 / AG / NIA NIH HHS / United States
R01 AG031581 / AG / NIA NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
HHSN268201500001C / HL / NHLBI NIH HHS / United States
P50 AG016574 / AG / NIA NIH HHS / United States
P50 AG005146 / AG / NIA NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
U01 AG049507 / AG / NIA NIH HHS / United States
U01 HL096917 / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
U01 AG052411 / AG / NIA NIH HHS / United States
R01 AG019085 / AG / NIA NIH HHS / United States
U01 AG032984 / AG / NIA NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
R01 AG013616 / AG / NIA NIH HHS / United States
R01 AG030146 / AG / NIA NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
U01 AG024904 / AG / NIA NIH HHS / United States
P50 AG008702 / AG / NIA NIH HHS / United States
UL1 RR029893 / RR / NCRR NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
U01 AG016976 / AG / NIA NIH HHS / United States
P50 NS039764 / NS / NINDS NIH HHS / United States
P01 AG003991 / AG / NIA NIH HHS / United States
P30 AG008051 / AG / NIA NIH HHS / United States
P50 AG005681 / AG / NIA NIH HHS / United States
RC2 AG036502 / AG / NIA NIH HHS / United States
R01 AG017917 / AG / NIA NIH HHS / United States
U01 HL096902 / HL / NHLBI NIH HHS / United States
P30 AG013846 / AG / NIA NIH HHS / United States
UF1 AG047133 / AG / NIA NIH HHS / United States
R01 MH080295 / MH / NIMH NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
R01 AG049607 / AG / NIA NIH HHS / United States
P50 AG005136 / AG / NIA NIH HHS / United States
P30 AG012300 / AG / NIA NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
R01 AG045775 / AG / NIA NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
R01 AG012101 / AG / NIA NIH HHS / United States
P50 AG016573 / AG / NIA NIH HHS / United States
R01 AG042475 / AG / NIA NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
P50 AG016570 / AG / NIA NIH HHS / United States
P50 AG005134 / AG / NIA NIH HHS / United States
P30 AG008017 / AG / NIA NIH HHS / United States
U24 AG041689 / AG / NIA NIH HHS / United States
P01 AG019724 / AG / NIA NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
P30 AG010161 / AG / NIA NIH HHS / United States
R01 AG033193 / AG / NIA NIH HHS / United States
P50 AG025688 / AG / NIA NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
R37 AG015473 / AG / NIA NIH HHS / United States
U24 AG026395 / AG / NIA NIH HHS / United States
HHSN268201500001I / HL / NHLBI NIH HHS / United States
U01 AG049508 / AG / NIA NIH HHS / United States
U01 AG052410 / AG / NIA NIH HHS / United States
R01 CA129769 / CA / NCI NIH HHS / United States
U01 HL096814 / HL / NHLBI NIH HHS / United States
P50 AG005133 / AG / NIA NIH HHS / United States
P01 AG002219 / AG / NIA NIH HHS / United States
RF1 AG059717 / AG / NIA NIH HHS / United States
U01 AG010483 / AG / NIA NIH HHS / United States
U01 AG006781 / AG / NIA NIH HHS / United States
R01 AG041797 / AG / NIA NIH HHS / United States
P50 AG005144 / AG / NIA NIH HHS / United States
P01 AG010491 / AG / NIA NIH HHS / United States
R01 AG033040 / AG / NIA NIH HHS / United States
P50 AG005138 / AG / NIA NIH HHS / United States
U54 HG003079 / HG / NHGRI NIH HHS / United States
U01 AG052409 / AG / NIA NIH HHS / United States
R01 AG021547 / AG / NIA NIH HHS / United States
R01 AG041232 / AG / NIA NIH HHS / United States
R01 AG019757 / AG / NIA NIH HHS / United States
R01 AG020688 / AG / NIA NIH HHS / United States
R01 AG020098 / AG / NIA NIH HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
R01 HL070825 / HL / NHLBI NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
R01 AG027944 / AG / NIA NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
R01 AG017173 / AG / NIA NIH HHS / United States
R01 AG025259 / AG / NIA NIH HHS / United States
R01 AG030653 / AG / NIA NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
U01 HL096899 / HL / NHLBI NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
U01 AG049506 / AG / NIA NIH HHS / United States
U01 HG004610 / HG / NHGRI NIH HHS / United States
/ WT_ / Wellcome Trust / United Kingdom
P30 AG010129 / AG / NIA NIH HHS / United States
P30 AG019610 / AG / NIA NIH HHS / United States
P50 AG016582 / AG / NIA NIH HHS / United States
R01 AG041718 / AG / NIA NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
P30 AG028383 / AG / NIA NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
R01 AG026916 / AG / NIA NIH HHS / United States
P50 AG033514 / AG / NIA NIH HHS / United States
R01 NS059873 / NS / NINDS NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
R01 AG057187 / AG / NIA NIH HHS / United States
U01 AG049505 / AG / NIA NIH HHS / United States

Theme by Danetsoft and Danang Probo Sayekti inspired by Maksimer