Defining the causes of sporadic Parkinson's disease in the global Parkinson's genetics program (GP2)

The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

A comparison of one-year treatment utilization for shoulder osteoarthritis patients initiating care with non-orthopaedic physicians and orthopaedic specialists

Abstract Background In this paper we investigate patients seeking care for a new diagnosis of shoulder osteoarthritis (OA) and the association between a patient’s initial physician specialty choice and one-year surgical and conservative treatment utilization. Methods Using retrospective data from a single large regional healthcare system, we identified 572 individuals with a new diagnosis of shoulder OA and identified the specialty of the physician which was listed as the performing physician on the index shoulder visit. We assessed treatment utilization in the year following the index shoulder visit for patients initiating care with a non-orthopaedic physician (NOP) or an orthopaedic specialist (OS). Descriptive statistics were calculated for each group and subsequent one-year surgical and conservative treatment utilization was compared between groups. Results Of the 572 patients included in the study, 474 (83%) received care from an OS on the date of their index shoulder visit, while 98 (17%) received care from a NOP. There were no differences in baseline patient age, gender, BMI or pain scores between groups. OS patients reported longer symptom duration and a higher rate of comorbid shoulder diagnoses. Patients initiating care with an OS on average received their first treatment much faster than patients initiating care with NOP (16.3 days [95% CI, 12.8, 19.7] vs. 32.3 days [95% CI, 21.0, 43.6], Z = 4.9, p < 0.01). Additionally, patients initiating care with an OS had higher odds of receiving surgery (OR = 2.65, 95% CI: 1.42, 4.95) in the year following their index shoulder visit. Conclusions Patients initiating care with an OS received treatment much faster and were treated with more invasive services over the year following their index shoulder visit. Future work should compare patient-reported outcomes across patient groups to assess whether more expensive and invasive treatments yield better outcomes for patients with shoulder OA

Defining the causes of sporadic Parkinson’s disease in the global Parkinson’s genetics program (GP2)

The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia

Multi-ancestry genome-wide association meta-analysis of Parkinson’s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations