Comprehensive Research Synopsis and Systematic Meta-Analyses in ALS Genetics: The ALSGene Database (P01.095)

Abstract

Objective: To facilitate interpretation of genetic association findings in amyotrophic lateral sclerosis (ALS) by creating a freely publicly available database aimed to serve as a comprehensive, unbiased, and regularly updated resource of genetic association studies in the field. Background ALS is a genetically complex and heterogeneous disorder. To date, mutations in several genes have been identified to cause familial forms of ALS. On the other hand, ALS without obvious familial aggregation is likely governed by a variety of genetic and non-genetic risk factors. In the past two decades, hundreds of reports, including several genome-wide association studies (GWAS), have been published claiming or refuting genetic association between certain genetic variants and susceptibility for ALS. Design/Methods: Using methodology developed earlier by our group (e.g. Bertram [2007] Nat Genet 39(1):17-23), database curation is currently ongoing and entails identifying and annotating published genetic association studies following systematic searches of scientific literature databases. Extracted data includes characteristics of the investigated populations as well as variant-specific results and genotyping details. In addition, we are in the process of including the results of several published GWAS derived from both observed and imputed genotype data. Up-to-date meta-analyses are presented for polymorphisms with data available in at least four independent case-control samples. Additional features of ALSGene will include the possibility to create custom meta-analyses (e.g. using existing or novel data), and an "ALSGene-Wiki" section (linking information on the potential molecular genetic and functional role of associated polymorphisms). Results: All data and results in ALSGene are freely available at www.alsgene.org. At the meeting, we will provide a detailed summary of the current "Top Results" including their potential relevance to ALS pathogenesis. Conclusions: Our systematic approach not only provides the most comprehensive account of non-Mendelian ALS genetics, but will also help prioritize future fine-mapping and functional genetic experiments

Assessing the lack of diversity in genetics research across neurodegenerative diseases: a systematic review of the GWAS Catalog and literature

“…Recently, more multi-ancestry studies have been conducted in PD, nominating novel loci for disease risk and age at onset including ITGA8, SV2C, and BST1 26,27,28 . The largest meta-GWAS for PD, which included 4 ancestral populations, identified 12 novel loci: MTF2, RP11-360P21.2, ADD1, SYBU, IRS2, USP8:RP11-562A8.5, PIGL, FASN, MYLK2, AJ006998.2, Y_RNA, and PPP6R2 7 .…”

Behavioral Neurobiology of Huntington's Disease and Parkinson's Disease

“…The relatively frequent G2019S mutation in LRRK2 has also been identified in 1-2 % of idiopathic PD cases and up to 40 % of patients with familial PD depending on ethnicity . Genome-wide association studies further indicate that common variation in the LRRK2 gene is a risk factor for idiopathic PD , International Parkinson Disease Genomics et al (2011), Lill et al (2012. Genome-wide association studies further indicate that common variation in the LRRK2 gene is a risk factor for idiopathic PD , International Parkinson Disease Genomics et al (2011), Lill et al (2012.…”