Joshua M Shulman

Massive-scale single-nucleus multi-omics identifies novel rare noncoding drivers of Parkinson's disease

The paper identifies rare noncoding variants associated with Parkinson's disease using multi-omic data from over 3.3 million nuclei.

Rare but Relevant: Assessing Variants in Dystonia-linked Genes in Parkinson's Disease

The paper assesses the frequency of dystonia-linked pathogenic variants in Parkinson's disease patients and finds they are present in 0.57% of cases, with GCH1 being the most common gene affected.

The Causal Pivot: A Structural Approach to Genetic Heterogeneity and Variant Discovery in Complex Diseases

The paper introduces the Causal Pivot (CP) method to detect causal genetic variants in complex diseases using structural causal models and applies it to UK Biobank data for three diseases.

Revealing the nervous system requirements of Alzheimer disease risk genes in Drosophila

This study identifies nervous system requirements for Alzheimer's disease risk genes in Drosophila by analyzing gene function and neurodegeneration.

Systems genetic dissection of Alzheimer's disease brain gene expression networks

This study uses a cross-species approach to identify gene expression networks linked to Alzheimer's disease pathology and neurodegeneration.

Tau polarizes an aging transcriptional signature to excitatory neurons and glia

The paper uses single-cell RNA-sequencing in Drosophila to show that tau pathology and aging affect different cell types, with tau primarily impacting excitatory neurons and glia.

Latent factor in Brain RNA-seq studies reflects cell type and clinical heterogeneity

The paper identifies a latent factor in brain RNA-seq data that reflects cell type and clinical heterogeneity, improving the identification of biological pathways and biomarkers.

Functional screening of lysosomal storage disorder genes identifies modifiers of alpha-synuclein mediated neurodegeneration

The paper identifies genetic modifiers of alpha-synuclein-mediated neurodegeneration by screening fly homologs of lysosomal storage disorder genes.

Genome sequencing in the Parkinson disease clinic

This study performs genome sequencing in Parkinson's disease patients and finds genetic variants in 3.4% for LRRK2 and 10.1% for GBA, with 82% of patients willing to share variants with relatives.

Human-lineage-specific genomic elements: relevance to neurodegenerative disease and APOE transcript usage

The paper identifies human-lineage-specific genomic elements, called CNCRs, and shows their enrichment in neurological disease genes and APOE intron-3 retention transcripts in Alzheimer's disease.

Genome-Wide Association Study Meta-Analysis for Parkinson Disease Motor Subtypes

This study identifies genetic associations with Parkinson disease motor subtypes using GWAS, finding novel variants and suggesting overlap with essential tremor genetics.

TBK1 interacts with tau and enhances neurodegeneration in tauopathy

This study identifies TBK1 as a tau-interacting kinase that enhances neurodegeneration in tauopathies through increased tau phosphorylation.

Integrated analysis of the aging brain transcriptome and proteome in tauopathy

The paper analyzes transcriptome and proteome changes in a Drosophila tauopathy model, identifying age- and Tau-induced gene expression differences and their cross-species implications.

A Consensus Proteomic Analysis of Alzheimer's Disease Brain and Cerebrospinal Fluid Reveals Early Changes in Energy Metabolism Associated with Microglia and Astrocyte Activation

The paper identifies protein network modules in Alzheimer's disease brains and cerebrospinal fluid that are associated with energy metabolism and neuroinflammation, suggesting potential biomarkers and therapeutic targets.

Regulatory sites for known and novel splicing in human basal ganglia are enriched for disease-relevant information

The paper identifies disease-relevant regulatory loci in human basal ganglia using genomic and transcriptomic data from 117 brains, highlighting splicing eQTLs and ASE analyses as sources of cell-specific regulatory information.

Integrated Sequencing & Array Comparative Genomic Hybridization in Familial Parkinson’s Disease

The paper combines exome sequencing and array-based comparative genomic hybridization to identify genetic risk factors in familial Parkinson’s disease, finding novel SNVs and CNVs.

Expanding Parkinson’s disease genetics: novel risk loci, genomic context, causal insights and heritable risk

Across 37,688 Parkinson's cases, 18,618 proxy-cases and 1.4M controls, 90 risk signals map to 78 loci (37 new); an 1805-variant polygenic score explains 26-36% of heritability.

Genetic modifiers of risk and age at onset in GBA associated Parkinson disease and Lewy body dementia

The paper identifies genetic modifiers of risk and age at onset in GBA-associated Parkinson disease and Lewy body dementia using large case-control datasets and genome-wide association studies.

Tau-mediated Disruption of the Spliceosome Triggers Cryptic RNA-splicing and Neurodegeneration in Alzheimer’s Disease

This study shows that Tau disrupts the spliceosome, leading to cryptic RNA splicing and neurodegeneration in Alzheimer’s disease.

Moving beyond neurons: the role of cell type-specific gene regulation in Parkinson’s disease heritability

This study connects Parkinson’s disease heritability to cell-type-specific gene regulation, finding enrichment in lysosomal genes in astrocytic and microglial subtypes rather than specific cell types or brain regions.

Parkinson disease age of onset GWAS: defining heritability, genetic loci and a-synuclein mechanisms

This study conducts a GWAS to identify genetic determinants of Parkinson's disease age of onset, finding associations with SNCA, TMEM175, and GBA, and highlighting alpha-synuclein's role in disease onset.

Functional dissection of Alzheimer’s disease brain gene expression signatures in humans and mouse models

The paper identifies gene expression signatures in human and mouse brains linked to Alzheimer's disease and finds species-specific and shared patterns across neurodegenerative models.

Meta-analysis of the human brain transcriptome identifies heterogeneity across human AD coexpression modules robust to sample collection and methodological approach

Coexpression meta-analysis of 2114 human brain RNA-seq samples across the AMP-AD consortium identifies five consensus Alzheimer's disease transcriptional clusters, including two sex-heterogeneous clusters and a previously unreported proteostasis cluster.