ABI3 and PLCG2 missense variants as risk factors for neurodegenerative diseases in Caucasians and African Americans.
Olivia J ConwayMinerva M CarrasquilloXue WangJenny M BredenbergJoseph S ReddySamantha L StricklandCurtis S YounkinJeremy D BurgessMariet AllenSarah J LincolnThuy NguyenKimberly G MalphrusAlexandra I SotoRonald L WaltonBradley F BoeveRonald C PetersenJohn A LucasTanis J FermanWilliam P CheshireJay A van GerpenRyan J UittiZbigniew K WszolekOwen A RossDennis W DicksonNeill R Graff-RadfordNilüfer Ertekin-TanerPublished in: Molecular neurodegeneration (2018)
We validated the associations previously reported with ABI3_rs616338-T and PLCG2_rs72824905-G in a Caucasian AD case-control cohort, and observed a similar direction of effect in DLB. Conversely, PLCG2_rs72824905-G showed suggestive associations with PSP and MSA in the opposite direction. We identified microglial gene-enriched co-expression networks with significantly higher levels in AD TCX, but not in PSP, a primary tauopathy. This co-expression network association appears to be driven by microglial cell population changes in a brain region affected by AD pathology. Although these findings require replication in larger cohorts, they suggest distinct effects of the microglial genes, ABI3 and PLCG2 in neurodegenerative diseases that harbor significant vs. low/no amyloid ß pathology.
Keyphrases
- poor prognosis
- inflammatory response
- lipopolysaccharide induced
- case control
- lps induced
- neuropathic pain
- copy number
- genome wide
- genome wide identification
- binding protein
- cell therapy
- resting state
- long non coding rna
- white matter
- spinal cord
- stem cells
- gene expression
- functional connectivity
- dna methylation
- cerebral ischemia
- african american
- bone marrow
- subarachnoid hemorrhage
- bioinformatics analysis