Alzheimer disease (AD) is the leading cause of dementia in older adults and occurs in all ethnic and racial groups. A multitude of studies have identified multiple AD associated genes and loci, but a large portion of the genetic contribution to AD remain unknown. The Alzheimer Disease Sequencing Project (ADSP) is using large-scale sequencing efforts to increase our knowledge about the genetic variation that influences AD, particularly rare genetic variants that enhance AD risk or protect against AD. A major initiative within the ADSP is the Follow Up Study (ADSP-FUS), an expansion of gene discovery efforts to include diverse and unique population. Over the past 12 months, the scope of the ADSP-FUS has expanded to include a number of new cohorts for sequencing. The inclusion of these new cohorts, which have a broad span of clinical-phenotype information, significantly enriches the value of the ADSP in achieving its goal of increasing knowledge of genetic variation in AD across different populations. This supplement is designed to complete pre-statistical harmonization activities in six new cohorts that will be included in the larger harmonization of clinical-phenotype data in all of the ADSP datasets. The final ADSP harmonized dataset, which includes all cohorts (and future cohorts) will create an invaluable, much needed, legacy resource for the NIA. We will perform comprehensive pre-harmonization activities for the six new FUS cohorts (Age, Gene/Environment Susceptibility (AGES) Study; Longitudinal Study of Aging in India-Diagnostic Assessment of Dementia (LASI-DAD); Gwangju Alzheimer and Related Dementias (GARD) Study; Long Life Family Study (LLFS); Aspirin in Reducing Events in the Elderly (ASPREE) Trial Cohort; Iberian Peninsula Cohort) that are not currently funded through other sources. Given that these cohorts vary in their focus (i.e., not all are dementia cohorts) there is a wide span of clinical-phenotype information which makes harmonization challenging. Creating a pre-statistical harmonization workflow in which these data are prepared and used by the ADSP-Harmonization Consortium will expedite the delivery of harmonized clinical-phenotype data to the larger AD community. To complete the pre-statistical harmonization efforts, we will: (a) Identify, collect and organize clinical-phenotype data from the new cohorts, (b) Review and document procedures for data collection for all relevant clinical-phenotype variables, and (c) Perform preliminary quality control analyses for cohort specific data. The successful completion of the proposed pre-statistical harmonization will yield harmonization ready data for the six cohorts that will be utilized in the statistical harmonization of all ADSP datasets. Just as important, this supplement will establish an infrastructure for implementing pre-statistical harmonization that will be integrated into the ADSP-Harmonization Consortium. In the long run, by enhancing harmonization of the ADSP cohorts we are helping make available valuable sequence data to the AD research community to speed gene discovery and identify targets for AD therapies.
We propose to perform pre-statistical harmonization on six new cohorts that are now included in the Alzheimer?s Disease Sequencing Project Follow Up Study (ADSP-FUS). Results from this effort will then be used by the ADSP-Harmonization Consortium as part of the larger harmonization of the ADSP-FUS and ultimately, all of the ADSP datasets. We will do this by (1) Identifying, collecting, and organizing all available clinical-phenotype data per the domains proposed by the ADSP-HC, (2) Organizing the information from SA1 in formats to allow for comparisons with existing harmonized data and to document progress, and (3). Performing preliminary quality control analyses on cohort specific data. This project will accelerate harmonization efforts in developing analysis ready phenotypic datasets for AD investigators to begin their gene search.
