Executive Committee-Cross Consortium Collaboration and Communication Committee (EC-4C)
The Executive Committee and Cross Consortium Collaboration and Communication Committee (EC-4C) is the governing body of the ADSP and is responsible for both ADSP administrative duties and enhancing collaborative efforts to meet the final goals of the ADSP. The chair of the EC-4C and two vice chairs serve a 2 year term. The main committee is comprised of 24 member. Two are at-large and the remaining are two representatives from each of the 12 constituent ADSP groups covering ADSP consortia and infrastructure. Changes in the composition of the EC-4C are expected over time so that it remains aligned with the evolving ADSP structure and maintains the stability of the committee. Each constituent ADSP group will designate its two representatives to serve on the EC-4C for a two-year renewable term.
Analysis Coordinating Group
The Analysis Coordinating Group (ACG) consists of senior PIs that make up the Executive Committee (EC) and other investigators from the ADSP. A primary function of the ACG is to exchange information on all activities of the ADSP and disperse that information to ADSP members.
Analysis Working Group
The goal of the Analysis Working Group is to provide a space for the discussion of behind-the-scenes details involved in the analysis of the complex ADSP data. This contrasts with the Analysis Coordination Group which is focused on keeping all investigators abreast of the analyses proposed and in process.
Structural Variants Working Group
The Structural variant (SV) workgroup is studying both indels (insertions and deletions) smaller than 50 bp and larger SVs that include deletions, duplications, and insertions, and balanced forms, such as inversions and translocations. Indels and SVs are responsible for diversity and evolution at individual and population levels. Due to their large size, SVs confer 5-10-fold higher heritable differences between individuals compared to SNVs (0.5–1% for SVs and 0.1% for SNVs). The SV workgroup discusses progress by multiple laboratories using multiple approaches. The group regularly discussed progress and characteristics of indel/SV call sets. The goal is to generate call sets by multiple methods with known specificity and sensitivity characteristics.
Protective Variants Working Group
The goal of the ADSP Protective Variants Working Group (PVWG) is to identify variants, genes, and genesets that modify the effect of known AD risk factors such as APOE-ε4, age, and sex. We are particularly interested in protective genetic factors as they represent high priority AD therapeutic targets. PVWG activities focus on: APOE extremes AD case-control association analyses to identify disease loci in age extremes x APOE genotype strata; Deviation from predicted risk association analyses to identify loci modifying outcomes predicted by AD risk models generated from APOE, age, and sex. We perform these analyses using multi-ethnic ADSP and AD genetics community sequencing and genotyping array datasets, as appropriate.
Gene Verification Committee
The Gene Verification Committee (GVC) is reviewing published human genetic evidence that specific loci or genes are associated with Alzheimer’s disease (AD) or contribute to AD risk. The GVC is focused on AD and dementia as phenotypes but includes AD-related phenotypes and AD endophenotypes. “AD” is defined as either clinical AD (probably) or definite AD (autopsy-documented). The committee will also consider “dementia” as a phenotype, to capture recent analyses based on biobank data. “Dementia” is less precisely defined as evidence of cognitive impairment. The committee is reviewing new publications for evidence of novel loci/genes and for evidence on genes/loci from prior reports. The committee is ranking evidence using a four-tier system, designating results as having sufficient, suggestive, limited, and insufficient evidence of an association. The goal of the GVC is to provide evaluation of the quality of evidence supporting loci and genes for AD/dementia so that functional genomics methods can be targeted to loci and genes supported by high-quality genetic evidence.