Pleiotropy with sex-specific traits reveals genetic aspects of sex differences in Parkinson's disease.

Parkinson's disease is an age-related neurodegenerative disorder with a higher incidence in males than females. The causes for this sex difference are unknown. Genome-wide association studies (GWAS) have identified 90 Parkinson's disease risk loci, but the genetic studies have not found sex-specific differences in allele frequency on autosomal chromosomes or sex chromosomes.

Transcriptomic profiling of Parkinson's disease brains reveals disease stage specific gene expression changes.

Parkinson´s disease (PD) is a progressive neurodegenerative disorder characterized by both motor and non-motor symptoms. Aggravation of symptoms is mirrored by accumulation of protein aggregates mainly composed by alpha-synuclein in different brain regions, called Lewy bodies (LB). Previous studies have identified several molecular mechanisms as autophagy and inflammation playing a role in PD pathogenesis.

Epigenome-wide association study of human frontal cortex identifies differential methylation in Lewy body pathology.

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are closely related progressive disorders with no available disease-modifying therapy, neuropathologically characterized by intraneuronal aggregates of misfolded α-synuclein. To explore the role of DNA methylation changes in PD and DLB pathogenesis, we performed an epigenome-wide association study (EWAS) of 322 postmortem frontal cortex samples and replicated results in an independent set of 200 donors. We report novel differentially methylated replicating loci associated with Braak Lewy body stage near TMCC2, SFMBT2, AKAP6 and PHYHIP.

and Are Associated With Dementia in Neuropathologically Confirmed Parkinson's Disease.

Cognitive decline and dementia are common and debilitating non-motor phenotypic features of Parkinson's disease with a variable severity and time of onset. Common genetic variation of the Apolipoprotein E () and micro-tubule associated protein tau () loci have been linked to cognitive decline and dementia in Parkinson's disease, although studies have yielded mixed results. To further elucidate the influence of and variability on dementia in Parkinson's disease, we genotyped postmortem brain tissue samples of clinically and pathologically well-characterized Parkinson's donors and performed a survival analysis of time to dementia.

Allele-specific expression of Parkinson's disease susceptibility genes in human brain.

Genome-wide association studies have identified genetic variation in genomic loci associated with susceptibility to Parkinson's disease (PD), the most common neurodegenerative movement disorder worldwide. We used allelic expression profiling of genes located within PD-associated loci to identify cis-regulatory variation affecting gene expression. DNA and RNA were extracted from post-mortem superior frontal gyrus tissue and whole blood samples from PD patients and controls.

A comprehensive analysis of SNCA-related genetic risk in sporadic parkinson disease.

Objective: The goal of this study was to refine our understanding of disease risk attributable to common genetic variation in SNCA, a major locus in Parkinson disease, with potential implications for clinical trials targeting α-synuclein. We aimed to dissect the multiple independent association signals, stratify individuals by SNCA-specific risk profiles, and explore expression quantitative trait loci.

Methods: We analyzed participant-level data from 12,503 patients and 12,502 controls, optimizing a risk model and assessing SNCA-specific risk scores and haplotypes as predictors of individual risk.

Friedreich ataxia in Norway - an epidemiological, molecular and clinical study.

Background: Friedreich ataxia is an autosomal recessive hereditary spinocerebellar disorder, characterized by progressive limb and gait ataxia due to proprioceptive loss, often complicated by cardiomyopathy, diabetes and skeletal deformities. Friedreich ataxia is the most common hereditary ataxia, with a reported prevalence of 1:20 000 - 1:50 000 in Central Europe. Previous reports from south Norway have found a prevalence varying from 1:100 000 - 1:1 350 000; no studies are previously done in the rest of the country.