- Home
- About
- Collaborative Data Access (SAGs)
- Publications
- For Members
Title | Initial assessment of the pathogenic mechanisms of the recently identified Alzheimer risk Loci. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Holton P, Ryten M, Nalls M, Trabzuni D, Weale ME, Hernandez D, Crehan H, J Gibbs R, Mayeux R, Haines JL, Farrer LA, Pericak-Vance MA, Schellenberg GD, Ramirez-Restrepo M, Engel A, Myers AJ, Corneveaux JJ, Huentelman MJ, Dillman A, Cookson MR, Reiman EM, Singleton A, Hardy J, Guerreiro R |
Corporate Authors | Alzheimer's Disease Genetics Consortium |
Journal | Ann Hum Genet |
Volume | 77 |
Issue | 2 |
Pagination | 85-105 |
Date Published | 2013 Mar |
ISSN | 1469-1809 |
Keywords | Aged, Aged, 80 and over, Alzheimer Disease, Brain, Chromosome Mapping, DNA Methylation, Female, Gene Frequency, Genetic Loci, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Risk Factors |
Abstract | Recent genome wide association studies have identified CLU, CR1, ABCA7 BIN1, PICALM and MS4A6A/MS4A6E in addition to the long established APOE, as loci for Alzheimer's disease. We have systematically examined each of these loci to assess whether common coding variability contributes to the risk of disease. We have also assessed the regional expression of all the genes in the brain and whether there is evidence of an eQTL explaining the risk. In agreement with other studies we find that coding variability may explain the ABCA7 association, but common coding variability does not explain any of the other loci. We were not able to show that any of the loci had eQTLs within the power of this study. Furthermore the regional expression of each of the loci did not match the pattern of brain regional distribution in Alzheimer pathology. Although these results are mainly negative, they allow us to start defining more realistic alternative approaches to determine the role of all the genetic loci involved in Alzheimer's disease. |
DOI | 10.1111/ahg.12000 |
Alternate Journal | Ann. Hum. Genet. |
PubMed ID | 23360175 |
PubMed Central ID | PMC3578142 |
Grant List | 081864 / / Wellcome Trust / United Kingdom 089703 / / Wellcome Trust / United Kingdom 100140 / / Wellcome Trust / United Kingdom AG010491 / AG / NIA NIH HHS / United States AG019757 / AG / NIA NIH HHS / United States AG021547 / AG / NIA NIH HHS / United States AG025688 / AG / NIA NIH HHS / United States AG027944 / AG / NIA NIH HHS / United States AG030653 / AG / NIA NIH HHS / United States AG05128 / AG / NIA NIH HHS / United States AG05144 / AG / NIA NIH HHS / United States G0802462 / / Medical Research Council / United Kingdom K01 AG030514 / AG / NIA NIH HHS / United States K23 AG034550 / AG / NIA NIH HHS / United States M01RR00096 / RR / NCRR NIH HHS / United States MH60451 / MH / NIMH NIH HHS / United States MR/J006742/1 / / Medical Research Council / United Kingdom NS39764 / NS / NINDS NIH HHS / United States P01 AG002219 / AG / NIA NIH HHS / United States P01 AG019724 / AG / NIA NIH HHS / United States P01 AG03991 / AG / NIA NIH HHS / United States P30 AG008017 / AG / NIA NIH HHS / United States P30 AG008051 / AG / NIA NIH HHS / United States P30 AG010124 / AG / NIA NIH HHS / United States P30 AG010129 / AG / NIA NIH HHS / United States P30 AG010133 / AG / NIA NIH HHS / United States P30 AG010161 / AG / NIA NIH HHS / United States P30 AG010161 / AG / NIA NIH HHS / United States P30 AG012300 / AG / NIA NIH HHS / United States P30 AG013846 / AG / NIA NIH HHS / United States P30 AG013854 / AG / NIA NIH HHS / United States P30 AG019610 / AG / NIA NIH HHS / United States P30 AG028377 / AG / NIA NIH HHS / United States P30 AG028383 / AG / NIA NIH HHS / United States P30 AG08051 / AG / NIA NIH HHS / United States P30 AG10133 / AG / NIA NIH HHS / United States P30 AG19610 / AG / NIA NIH HHS / United States P30AG10161 / AG / NIA NIH HHS / United States P50 AG005131 / AG / NIA NIH HHS / United States P50 AG005133 / AG / NIA NIH HHS / United States P50 AG005133 / AG / NIA NIH HHS / United States P50 AG005134 / AG / NIA NIH HHS / United States P50 AG005136 / AG / NIA NIH HHS / United States P50 AG005138 / AG / NIA NIH HHS / United States P50 AG005142 / AG / NIA NIH HHS / United States P50 AG005146 / AG / NIA NIH HHS / United States P50 AG005681 / AG / NIA NIH HHS / United States P50 AG008671 / AG / NIA NIH HHS / United States P50 AG008702 / AG / NIA NIH HHS / United States P50 AG008702 / AG / NIA NIH HHS / United States P50 AG016570 / AG / NIA NIH HHS / United States P50 AG016573 / AG / NIA NIH HHS / United States P50 AG016573 / AG / NIA NIH HHS / United States P50 AG016574 / AG / NIA NIH HHS / United States P50 AG016575 / AG / NIA NIH HHS / United States P50 AG016576 / AG / NIA NIH HHS / United States P50 AG016577 / AG / NIA NIH HHS / United States P50 AG016582 / AG / NIA NIH HHS / United States P50 AG023501 / AG / NIA NIH HHS / United States P50-AG08671 / AG / NIA NIH HHS / United States R01 AG015819 / AG / NIA NIH HHS / United States R01 AG017173 / AG / NIA NIH HHS / United States R01 AG019085 / AG / NIA NIH HHS / United States R01 AG020688 / AG / NIA NIH HHS / United States R01 AG025259 / AG / NIA NIH HHS / United States R01 AG026916 / AG / NIA NIH HHS / United States R01 AG027944 / AG / NIA NIH HHS / United States R01 AG031581 / AG / NIA NIH HHS / United States R01 AG034504 / AG / NIA NIH HHS / United States R01 AG040770 / AG / NIA NIH HHS / United States R01 AG15819 / AG / NIA NIH HHS / United States R01 AG17917 / AG / NIA NIH HHS / United States R01 AG30146 / AG / NIA NIH HHS / United States R01 CA129769 / CA / NCI NIH HHS / United States R01 MH080295 / MH / NIMH NIH HHS / United States R01 NS059873 / NS / NINDS NIH HHS / United States R01 NS059873 / NS / NINDS NIH HHS / United States R01 NS059873] / NS / NINDS NIH HHS / United States R01AG15819 / AG / NIA NIH HHS / United States R01AG33193 / AG / NIA NIH HHS / United States R37 AG015473 / AG / NIA NIH HHS / United States RC2 AG036528 / AG / NIA NIH HHS / United States RC2 AG036535 / AG / NIA NIH HHS / United States U01 AG006781 / AG / NIA NIH HHS / United States U01 AG016976 / AG / NIA NIH HHS / United States U01 AG016976 / AG / NIA NIH HHS / United States U01 AG024904 / AG / NIA NIH HHS / United States U01 AG032984 / AG / NIA NIH HHS / United States U01 AG032984 / AG / NIA NIH HHS / United States U01 AG06781 / AG / NIA NIH HHS / United States U01 AG10483 / AG / NIA NIH HHS / United States U01 HG004610 / HG / NHGRI NIH HHS / United States U24 AG021886 / AG / NIA NIH HHS / United States U24 AG021886 / AG / NIA NIH HHS / United States U24 AG026390 / AG / NIA NIH HHS / United States U24 AG026395 / AG / NIA NIH HHS / United States UL1 RR029893 / RR / NCRR NIH HHS / United States UL1RR02777 / RR / NCRR NIH HHS / United States Z01 AG000950-06 / AG / NIA NIH HHS / United States Z01-AG000950-10 / AG / NIA NIH HHS / United States ZIA AG000950-10 / AG / NIA NIH HHS / United States / / Canadian Institutes of Health Research / Canada / / Howard Hughes Medical Institute / United States / / Medical Research Council / United Kingdom / / Wellcome Trust / United Kingdom |