Open AccessGenomics implicates adaptive and innate immunity in Alzheimer's and Parkinson's diseases
Author(s) -
Gagliano Sarah A.,
Pouget Jennie G.,
Hardy John,
Knight Jo,
Barnes Michael R.,
Ryten Mina,
Weale Michael E.
Publication year - 2016
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.369
Subject(s) - genome wide association study , immune system , amyotrophic lateral sclerosis , acquired immune system , innate immune system , heritability , disease , parkinson's disease , medicine , missing heritability problem , multiple sclerosis , biology , gene , immunology , genetics , pathology , genotype , single nucleotide polymorphism
Objectives We assessed the current genetic evidence for the involvement of various cell types and tissue types in the etiology of neurodegenerative diseases, especially in relation to the neuroinflammatory hypothesis of neurodegenerative diseases. Methods We obtained large‐scale genome‐wide association study ( GWAS ) summary statistics from Parkinson's disease ( PD ), Alzheimer's disease ( AD ), and amyotrophic lateral sclerosis ( ALS ). We used multiple sclerosis ( MS ), an autoimmune disease of the central nervous system, as a positive control. We applied stratified LD score regression to determine if functional marks for cell type and tissue activity, and gene‐set lists were enriched for genetic heritability. We compared our results to those from two gene‐set enrichment methods (Ingenuity Pathway Analysis and enrichr). Results There were no significant heritability enrichments for annotations marking genes active within brain regions, but there were significant heritability enrichments for annotations marking genes active within cell types that form part of both the innate and adaptive immune systems. We found this for MS (as expected) and also for AD and PD . The strongest signals were from the adaptive immune system (e.g., T cells) for PD , and from both the adaptive (e.g., T cells) and innate (e.g., CD 14: a marker for monocytes, and CD 15: a marker for neutrophils) immune systems for AD . Annotations from the liver were also significant for AD . Pathway analysis provided complementary results. Interpretation For AD and PD, we found significant enrichment of heritability in annotations marking gene activity in immune cells.