Genomics implicates adaptive and innate immunity in Alzheimer's and Parkinson's

TY - JOUR

T1 - Genomics implicates adaptive and innate immunity in Alzheimer's and Parkinson's

AU - Gagliano, Sarah A

AU - Pouget, Jennie G

AU - Hardy, John

AU - Knight, Jo

AU - Barnes, Michael R

AU - Ryten, Mina

AU - Weale, Michael E

PY - 2016/9/27

Y1 - 2016/9/27

N2 - Objectives: We assessed the current genetic evidence for the involvement of various cell types and tissue types in the aetiology of neurodegenerative diseases, especially in relation to the neuroinflammatory hypothesis of neurodegenerative diseases. Methods: We obtained large-scale genome-wide association (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 a gene-set enrichment method (Ingenuity Pathway Analysis). Results: There were no significant enrichments for annotations marking genes active within brain regions, but there were 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. CD14: a marker for monocytes, and CD15: a marker for neutrophils) immune systems for AD. Annotations from the liver were also significant for AD. Pathway analysis provided complementary results. Interpretation: For Alzheimer's and Parkinson's disease, we found significant enrichment of heritability in annotations marking gene activity in immune cells.

AB - Objectives: We assessed the current genetic evidence for the involvement of various cell types and tissue types in the aetiology of neurodegenerative diseases, especially in relation to the neuroinflammatory hypothesis of neurodegenerative diseases. Methods: We obtained large-scale genome-wide association (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 a gene-set enrichment method (Ingenuity Pathway Analysis). Results: There were no significant enrichments for annotations marking genes active within brain regions, but there were 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. CD14: a marker for monocytes, and CD15: a marker for neutrophils) immune systems for AD. Annotations from the liver were also significant for AD. Pathway analysis provided complementary results. Interpretation: For Alzheimer's and Parkinson's disease, we found significant enrichment of heritability in annotations marking gene activity in immune cells.

U2 - 10.1101/059519

DO - 10.1101/059519

M3 - Article

JO - Annals of Clinical and Translational Neurology

JF - Annals of Clinical and Translational Neurology

ER -