Core G: Genetics and Molecular Profiling

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Many recent advances in genetics and genomics technologies and rapid growth in knowledge of genetic risk factors for Alzheimer disease (AD) reinforce the importance of and opportunities for incorporating genetic information and designs into AD research. The Genetics & Molecular Profiling (GMP) Core will support genetics and `omics research by ADRC investigators, trainees and established investigators who are “breaking in” to AD research, and to build foundations for translational studies using ADRC resources. Given the centrality of genetics and `omics data to diverse scientific areas, unrealistic expectations that most AD researchers are capable and can afford to generate such data, and importance of avoiding costly duplicative data generation in order to preserve limited and precious specimen resources, the GMP Core will generate an array of genetic and `omic data. Although the GMP Core is a new component of the ADRC, it will build on our work of genetic and molecular characterization of BU ADC participants and other cohorts that has led to numerous important discoveries and greatly increased our understanding of mechanisms and biological pathways leading to AD. We will continue to serve as a centralized resource for the organization and analysis of genetic data within the ADRC and ADRC affiliated projects by providing an infrastructure needed to coordinate molecular research efforts that will lead to a better understanding of genotype-phenotype relationships for dementia and related endophenotypes. Specifically, the GMP Core will (1) process, extract DNA and RNA, store and distribute genetic material extracted from biological specimens (e.g., blood, brain, saliva) obtained from ADRC participants; (2) generate genome-wide array, DNA and RNA sequence, epigenetic and lipidomic data for use by ADRC and other BU investigators, as well as the scientific community; (3) track the collection and usage of genetic material; (4) manage all genetic and `omic data in collaboration with the Data Management & Statistics (DMS) Core; (5) maintain an integrated genetic and `omic database includes all genetic and `omic data generated from BU ADRC samples, as well as working libraries of extant genetic and `omic data; these data will be available with proper permissions as a resource for genetic analyses with guidance from the core investigators. The GMP Core will also facilitate access to an extensive set of genetic and genomic data from extant datasets that are available to the Core investigators including individual level and/or summarized data from the ADGC, ADSP, ADNI, AMP- AD, and UK Biobank; and (5) provide support for designing genetic and genomic studies, as well as for data analysis. In line with our vision for precision medicine, this profiling integrated with the extensive characterization performed in the Clinical, Biomarker and Neuropathology Cores will facilitate both agnostic and hypothesis- driven research. The Core will also partner with existing investigator-initiated research at Boston University (BU) and with the other Cores to strengthen existing programs and accelerate the incorporation of genetics and `omics into dementia research conducted by ADRC-affiliated as well as other BU investigators.