A Comprehensive Study of Circulating Blood Linear RNA nominates and as novel causal genes and early-stage biomarkers for Parkinson's Disease.

We leveraged transcriptomic data from 4,343 participants from four independent datasets to robustly identify and annotate circulating PD-associated transcripts. We identified 296 differentially expressed transcripts, 28 of which were transcribed from known PD-associated loci. Further, we found a significant overlap between our findings and transcripts dysregulated in brain, as well as proteins differentially accumulated in CSF.

Circulating blood circular RNA in Parkinson's Disease; from involvement in pathology to diagnostic tools in at-risk individuals.

To identify circRNAs associated with Parkinson's disease (PD) we leveraged two of the largest publicly available studies with longitudinal clinical and blood transcriptomic data. We performed a cross-sectional study utilizing the last visit of each participant (N = 1848), and a longitudinal analysis that included 1166 participants with at least two time points. We identified 192 differentially expressed circRNAs, with effects that were sustained during disease, in mutation carriers, and diverse ancestry.

Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer's disease.

The integration of quantitative trait loci (QTLs) with disease genome-wide association studies (GWASs) has proven successful in prioritizing candidate genes at disease-associated loci. QTL mapping has been focused on multi-tissue expression QTLs or plasma protein QTLs (pQTLs). We generated a cerebrospinal fluid (CSF) pQTL atlas by measuring 6,361 proteins in 3,506 samples.

Proteome wide association studies of LRRK2 variants identify novel causal and druggable proteins for Parkinson's disease.

Common and rare variants in the LRRK2 locus are associated with Parkinson's disease (PD) risk, but the downstream effects of these variants on protein levels remain unknown. We performed comprehensive proteogenomic analyses using the largest aptamer-based CSF proteomics study to date (7006 aptamers (6138 unique proteins) in 3107 individuals). The dataset comprised six different and independent cohorts (five using the SomaScan7K (ADNI, DIAN, MAP, Barcelona-1 (Pau), and Fundació ACE (Ruiz)) and the PPMI cohort using the SomaScan5K panel).

Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and informs causal proteins for Alzheimer's disease.

The integration of quantitative trait loci (QTL) with disease genome-wide association studies (GWAS) has proven successful at prioritizing candidate genes at disease-associated loci. QTL mapping has mainly been focused on multi-tissue expression QTL or plasma protein QTL (pQTL). Here we generated the largest-to-date cerebrospinal fluid (CSF) pQTL atlas by analyzing 7,028 proteins in 3,107 samples.

Functional screening of lysosomal storage disorder genes identifies modifiers of alpha-synuclein neurotoxicity.

Heterozygous variants in the glucocerebrosidase (GBA) gene are common and potent risk factors for Parkinson's disease (PD). GBA also causes the autosomal recessive lysosomal storage disorder (LSD), Gaucher disease, and emerging evidence from human genetics implicates many other LSD genes in PD susceptibility. We have systemically tested 86 conserved fly homologs of 37 human LSD genes for requirements in the aging adult Drosophila brain and for potential genetic interactions with neurodegeneration caused by α-synuclein (αSyn), which forms Lewy body pathology in PD.

Two Genomic Loci Control Three Eye Colors in the Domestic Pigeon (Columba livia).

The iris of the eye shows striking color variation across vertebrate species, and may play important roles in crypsis and communication. The domestic pigeon (Columba livia) has three common iris colors, orange, pearl (white), and bull (dark brown), segregating in a single species, thereby providing a unique opportunity to identify the genetic basis of iris coloration. We used comparative genomics and genetic mapping in laboratory crosses to identify two candidate genes that control variation in iris color in domestic pigeons.

Inadvertent Disabling of Implantable Cardiac Defibrillator Antitachycardia Therapies Following Breast Reconstructive Surgery.

A 47-year-old woman with an implantable cardiac defibrillator and breast cancer underwent left breast mastectomy with simultaneous reconstruction using a breast tissue expander. She was found to have intermittent disabling of tachyarrhythmia detection and therapy functions of her implantable cardiac defibrillator that were triggered by the breast tissue expander magnetic port.