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Initial Assessment of the Pathogenic Mechanisms of the Recently Identified Alzheimer Risk Loci
Author(s) -
Holton Patrick,
Ryten Mina,
Nalls Michael,
Trabzuni Daniah,
Weale Michael E.,
Hernandez Dena,
Crehan Helen,
Gibbs J. Raphael,
Mayeux Richard,
Haines Jonathan L.,
Farrer Lindsay A.,
PericakVance Margaret A.,
Schellenberg Gerard D.,
RamirezRestrepo Manuel,
Engel Anzhelika,
Myers Amanda J.,
Corneveaux Jason J.,
Huentelman Matthew J.,
Dillman Allissa,
Cookson Mark R.,
Reiman Eric M.,
Singleton Andrew,
Hardy John,
Guerreiro Rita
Publication year - 2013
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/ahg.12000
Subject(s) - expression quantitative trait loci , genome wide association study , biology , genetic association , apolipoprotein e , disease , quantitative trait locus , genetics , alzheimer's disease , gene , single nucleotide polymorphism , genotype , medicine , pathology
Summary 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.