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Genetic Variation in Genes Underlying Diverse Dementias May Explain a Small Proportion of Cases in the Alzheimer's Disease Sequencing Project.
Wednesday,2018-09-19 10:23 America/Los_Angeles — ecterry
| Title | Genetic Variation in Genes Underlying Diverse Dementias May Explain a Small Proportion of Cases in the Alzheimer's Disease Sequencing Project. |
| Publication Type | Journal Article |
| Year of Publication | 2018 |
| Authors | Blue, EE, Bis, JC, Dorschner, MO, Tsuang, DW, Barral, SM, Beecham, G, Below, JE, Bush, WS, Butkiewicz, M, Cruchaga, C, DeStefano, A, Farrer, LA, Goate, A, Haines, J, Jaworski, J, Jun, G, Kunkle, B, Kuzma, A, Lee, JJ, Lunetta, KL, Ma, Y, Martin, E, Naj, A, Nato, AQ, Navas, P, Nguyen, H, Reitz, C, Reyes, D, Salerno, W, Schellenberg, GD, Seshadri, S, Sohi, H, Thornton, TA, Valadares, O, van Duijn, C, Vardarajan, BN, San Wang, L-, Boerwinkle, E, Dupuis, J, Pericak-Vance, MA, Mayeux, R, Wijsman, EM |
| Corporate/Institutional Authors | on behalf of the Alzheimer’s Disease Sequencing Project |
| Journal | Dement Geriatr Cogn Disord |
| Volume | 45 |
| Issue | 1-2 |
| Pagination | 1-17 |
| Date Published | 2018 |
| ISSN | 1421-9824 |
| Abstract | <p><b>BACKGROUND/AIMS: </b>The Alzheimer's Disease Sequencing Project (ADSP) aims to identify novel genes influencing Alzheimer's disease (AD). Variants within genes known to cause dementias other than AD have previously been associated with AD risk. We describe evidence of co-segregation and associations between variants in dementia genes and clinically diagnosed AD within the ADSP.</p><p><b>METHODS: </b>We summarize the properties of known pathogenic variants within dementia genes, describe the co-segregation of variants annotated as "pathogenic" in ClinVar and new candidates observed in ADSP families, and test for associations between rare variants in dementia genes in the ADSP case-control study. The participants were clinically evaluated for AD, and they represent European, Caribbean Hispanic, and isolate Dutch populations.</p><p><b>RESULTS/CONCLUSIONS: </b>Pathogenic variants in dementia genes were predominantly rare and conserved coding changes. Pathogenic variants within ARSA, CSF1R, and GRN were observed, and candidate variants in GRN and CHMP2B were nominated in ADSP families. An independent case-control study provided evidence of an association between variants in TREM2, APOE, ARSA, CSF1R, PSEN1, and MAPT and risk of AD. Variants in genes which cause dementing disorders may influence the clinical diagnosis of AD in a small proportion of cases within the ADSP.</p> |
| DOI | 10.1159/000485503 |
| Alternate Journal | Dement Geriatr Cogn Disord |
| PubMed ID | 29486463 |
| PubMed Central ID | PMC5971141 |
| Grant List | HHSN268201100012C / HL / NHLBI NIH HHS / United States RC2 HL102419 / HL / NHLBI NIH HHS / United States HHSN268201100009I / HL / NHLBI NIH HHS / United States P30 AG010124 / AG / NIA NIH HHS / United States U54 AG052427 / AG / NIA NIH HHS / United States U54 HG003067 / HG / NHGRI NIH HHS / United States HHSN268201100010C / HL / NHLBI NIH HHS / United States P50 AG005131 / AG / NIA NIH HHS / United States R01 AG015928 / AG / NIA NIH HHS / United States U24 AG021886 / AG / NIA NIH HHS / United States HHSN268201100008C / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States I01 BX000531 / BX / BLRD VA / United States HHSN268201100005G / HL / NHLBI NIH HHS / United States U01 AG049507 / AG / NIA NIH HHS / United States HHSN268201100008I / HL / NHLBI NIH HHS / United States U01 AG052411 / 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 HHSN268200800007C / HL / NHLBI NIH HHS / United States R01 NS065070 / NS / NINDS 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 UF1 AG047133 / AG / NIA NIH HHS / United States P50 NS053488 / NS / NINDS NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States U54 HG003273 / HG / NHGRI NIH HHS / United States P50 AG005136 / AG / NIA NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States HHSN268201100006C / HL / NHLBI NIH HHS / United States U24 AG041689 / AG / NIA NIH HHS / United States P30 AG008017 / 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 HHSN268201100005I / HL / NHLBI NIH HHS / United States R37 AG015473 / AG / NIA NIH HHS / United States U01 AG049508 / AG / NIA NIH HHS / United States U01 AG052410 / AG / NIA NIH HHS / United States P50 AG005133 / AG / NIA NIH HHS / United States P50 NS062684 / NS / NINDS NIH HHS / United States U01 AG006781 / AG / NIA NIH HHS / United States U54 HG003079 / HG / NHGRI NIH HHS / United States R01 AG020098 / AG / NIA NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States HHSN268201100009C / HL / NHLBI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States HHSN268201100005C / HL / NHLBI NIH HHS / United States R01 NS048595 / NS / NINDS NIH HHS / United States HHSN268201100007I / HL / NHLBI NIH HHS / United States RF1 AG015473 / AG / NIA NIH HHS / United States U01 AG049506 / 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 N01HC85081 / HL / NHLBI NIH HHS / United States U01 AG049505 / AG / NIA NIH HHS / United States |
ePub date:
18/06