The Collaborative Study on the Genetics of Alcoholism (COGA) is a tightly integrated and interdisciplinary project, whose overarching goals are to understand the contributions and interactions of genetic, neurobiological, and social-environmental influences on the course of AUD, remission, and recurrence over the lifespan. COGA is a study of large, diverse families, many densely affected by AUD; family members have been characterized in clinical, behavioral, neurophysiological, neuropsychological, and social-environmental domains, yielding a rich phenotypic dataset paired with a large repository of biospecimens and genomewide data in 12,145 family members, as well as molecular and cellular genomic data that provide functional insights. With recent reports of increased heavy alcohol use and AUD in those ages 40 and older, it is critical that we gain a deeper understanding of the risk and resilience factors throughout the course of AUD during this period of the lifespan, and alcohol-related consequences (e.g., mental and physical health problems, cognitive decline, early mortality). COGA builds on the key strengths of our research achievements over the past 35 years and will now focus on adding new multi-domain data collection in those aged 40 and older to expand the longitudinal data available in our sample as they enter later life. The breadth and depth of longitudinal assessments in COGA families allow a fully panoramic view of the course of AUD, remission and recurrence and its consequences, enabling genomic analyses to be conducted within lifetime accumulation of risk and protective influences. In response to RFA-AA-24-003, we propose three inter-related and inter-dependent projects (Lifespan, Brain Function, Genomics) supported by three essential cores (NIAAA-COGA Sharing Repository (NCSR), Data Management and Coordination (DMC), and Administrative). Consistent with the RFA and in keeping with COGA’s research agenda, the overarching specific aims for the next five years are: Aim 1: Advance our understanding of the longitudinal course of alcohol use and AUD, and its adverse outcomes by studying genetic and social-environmental factors across the lifespan. Aim 2: Examine how the course of AUD and remission shapes brain functioning across the lifespan, and its consequences in later life, and the role of genetic and social-environmental factors in AUD-related brain function. Aim 3: Integrate genetic, genomic and functional studies to characterize AUD trajectories and related mental, behavioral and brain health outcomes across the lifespan. COGA’s multi-pronged approach, long history of productive collaboration among investigators, and commitment to data sharing, will allow us to propel the alcohol research field towards actionable findings that can be positioned to translate science to population health and clinical care. This advancement of science is only possible within a U10 mechanism that supports effective collaboration, integration and s...