Project 4 -- MIDUS Genomics Project

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ABSTRACT – GENOMICS PROJECT The MIDUS Genomics Project provides genomic data resources, analytic tools, and methodological training to advance the overall MIDUS objective of defining the relationship between psychosocial factors and health- and aging-related outcomes. Resources provided by this project include: 1) twin-based research strategies to identify overall genetic influences on psychosocial and health outcomes; 2) genome-wide RNA profiles to identify the specific gene expression pathways that mediate these influences; 3) genome-wide DNA methylation profiles to identify the specific epigenetic pathways that mediate these influences; 4) genome-wide single-nucleotide polymorphism profiles to identify the role of specific genetic polymorphisms and polygenic risk profiles; 5) targeted genotyping of specific gene variants of particular relevance to MIDUS research objectives, such as the APOE gene associated with Alzheimer’s Disease; and 6) training to MIDUS investigators in the special substantive and analytic aspects of genomic data. Genomic measures are collected from approximately 1200 participants in the MIDUS Biomarker Project (Core MIDUS and MIDUS Refresher samples), and include 2 waves of RNA and DNA methylation profiles that can quantify rates of biological aging and change over time in inflammatory biology and antiviral biology. Aims of the MIDUS Genomics Project include: Aim 1: Collect and disseminate RNA gene expression profiles, DNA methylation profiles, and targeted genotyping data; Aim 2: Analyze the relationship between psychosocial risk processes (e.g., socio-economic and socio-relational disadvantage) and resilience processes (e.g., psychological well- being and social resources), and longitudinal rates of change in the “Conserved Transcriptional Response to Adversity” (CTRA) RNA profile and DNA methylation measures of “epigenetic age” and mortality risk; Aim 3: Define the relationship between CTRA gene expression and epigenetic age acceleration to determine their correlation and respective relationships to health, well-being, and disease risk. The genomic data provided by this project provide essential genetic and molecular elements of MIDUS’s overall integrative biopsychosocial characterization of health and well-being of mid-life Americans.