RESEARCHING EPIGENETICS, WEATHERING, AGING & RESIDENTIAL DISADVANTAGE (REWARD)
This project aims to examine patterns of DNA methylation, a key epigenetic mechanism that influences gene expression during development and throughout life in response to environmental and social conditions. Specifically, it examines whether and how personal and neighborhood-level disadvantages impact methylation patterns associated with accelerated biological aging and inflammation, and chronic cardiovascular and metabolic disease outcomes.
PRINCIPAL INVESTIGATORS: Kristen Malecki and Michael Engelman
CO-INVESTIGATORS: Katherine Curtis, Corinne Engelman, Qiongshi Lu
NIH Grant Number: R01 AG061080
The Importance of Place of Birth in Determining Old Age Cognitive Health
This project aims to increase understanding of the impacts of early life geographic context on the levels of and disparities in old age cognitive health and Alzheimer’s Disease related mortality by using newly available data on millions of individuals linked to their state/county of birth over the 20th century. It identifies the contribution of environment experienced in childhood to variation in health and mortality by birth cohort, race/ethnicity, sex, and educational attainment. The projects will provide new evidence of the magnitude and mechanisms linking place of birth to disparities in AD/ADRD mortality and related morbidities over the life course in the US.
PRINCIPAL INVESTIGATORS: Jason Fletcher, Alberto Palloni
CO-INVESTIGATORS: Lindsay Clark, Michal Engelman, Malia Jones
NIH Grant Number: RF1AG062765
Educational and Early Life Predictors of Mild Cognitive Impairment: New Evidence about Mediators and Moderators from High School & Beyond
Researchers at UW are part of a research team studying the impacts of education on cognitive functioning in later life. This project will bring together sociologists, neuropsychologists, epidemiologists, and survey researchers to re-interview and collect genetic information from the 25,000 surviving members of the High School & Beyond Cohort. By studying these unique and rich data, the team hopes to better understand the implications of educational opportunities, conditions, and achievements for cognitive functioning and impairment in later life.
PRINCIPAL INVESTIGATOR: John Robert Warren (University of Minnesota)
UW-MADISON SUBPROJECT PI: Eric Grodsky
NIH Grant Number: R01 AG058719
Wisconsin Longitudinal Study – Initial Lifetime’s Impact on Alzheimer’s Disease and Related Dementias (WLS-ILIAD Study)
A team of researchers and clinicians has begun tracking the progression into dementia (AD dementia, non-AD dementia) of participants in the Wisconsin Longitudinal Study (WLS), one of the nation’s longest running longitudinal cohort studies – with nearly 60 years duration. The project will clarify the influence of the early life period on dementia risk—as well as adult behaviors that can offset risk. The findings from these aims will provide supporting evidence for policy and individual level interventions that could modify the risk for AD/ADRD.
PRINCIPAL INVESTIGATORS: Sanjay Asthana, Pamela Herd
CO-INVESTIGATORS: Robert Hauser, Amy Kind, Carol Roan
NIH Grant Number: R01 AG060737
The Importance of Place in Determining the Health and Mortality at Older Ages
This project aims to increase understanding of the impacts of early life geographic context on the levels of and variation of old age health, disability, and mortality by using newly available data on millions of individuals linked to their state/county of birth over the 20th century. It identifies the contribution of environment experienced in childhood to variation in health late in life by birth cohort, race/ethnicity, sex, and educational attainment. It also explores how early disease environments, cumulative contextual disadvantages, and life course mobility affect old age health outcomes. We will leverage newly released and unique longitudinal data on millions of individuals across multiple datasets containing rich measures of health processes in old age and mechanisms of early disease exposures, cumulative contextual disadvantage, and life course mobility. Using these data, we will create an “Atlas of Birth Place Impacts on Mortality and Morbidity at Older Ages”, determine the Influence of Birth Place on Health Disparities and Mortality Variation at Older Ages by sex, race/ethnicity, and education and uncover mechanisms linking the relationship between place of birth and later health by focusing on mobility and early and cumulative exposures. Together, these aims will allow a paradigm shift in how we understand old age health processes by integrating life course and spatial analysis into large scale analyses of the patterns and mechanisms of old age health and mortality.
Principal Investigators: Jason Fletcher, Alberto Palloni
Co-Investigators: Michal Engelman, Malia Jones, Katherine Curtis
NIH Grant Number: R01 AG060109
Applying Biodemography Methods to Advance our Understanding of Socioeconomic Risk Factors for Alzheimer’s Disease
This project includes a set of projects that will integrate findings from genetics, education research, health economics, and econometrics to estimate the causal effects of educational attainment on Alzheimer’s Disease (AD) related outcomes in two datasets. A second aim expands this analysis by focusing on the possible causal effects of sleep and loneliness on AD and cognitive health. Using newly available genetic data in the Health and Retirement Study and the UK Biobank, we will combine insights from genomic science and econometrics to uncover causal estimates in the form of genetic instrumental variables (GIV).
Principal Investigator: Jason Fletcher
Co-Investigators: Hyunseung Kang, Qiongshi Lu
NIH Grant Number: P30AG017266-20S
Understanding the Importance of Place of Birth on Alzheimer’s Disease Outcomes in the US and UK
This project aims to increase understanding of the impacts of early life geographic context on the levels of and disparities in old age cognitive health and Alzheimer’s Disease (AD) diagnosis and mortality by using newly available data on millions of individuals linked to their place of birth over the 20th century in the US and UK. It also explores how early contextual disadvantages and life course mobility affect these old age health outcomes. We plan to create an “Atlas of Birth Place Impacts on AD/ADRD Outcomes” which will allow us to uncover mechanisms linking the relationship between place of birth and later health by focusing on mobility and early exposures. Together, these aims will allow a paradigm shift in how we understand old age health processes by integrating life course and spatial analysis into large scale analyses of the patterns and mechanisms of old age cognitive health and AD/ADRD diagnosis and mortality outcomes
Principal Investigator: Jason Fletcher
Co-Investigators: Michal Engelman, Qiongshi Lu, Alberto Palloni
NIH Grant Number: R01AG060109-01S1
Wisconsin Longitudinal Study 2020 and Beyond
In this project, a team of researchers will expand the Wisconsin Longitudinal Study (WLS) in four ways. First, data from class of 1957 graduates not resurveyed in WLS will be digitized in order to contextualize the school and peer environments of the 10,000 respondents who were followed in the WLS for the past 50 years. Second, these digitized surveys will be linked to the 1940 census in order to infuse new measures of early childhood environments. Third, the surveys will be linked to mortality records, allowing researchers to examine how early exposures to pollution and toxicants predict mortality. Finally, the new project will explore the possibilities of linking the full 30,000 respondents to recent census products through the Wisconsin Federal Statistical Research Data Center.
PRINCIPAL INVESTIGATOR: Jason Fletcher
CO-INVESTIGATORS: Carol Roan, Sanjay Asthana, Marsha Mailick, James Raymo, and Nora Cate Schaeffer
More than five million Americans are living with Alzheimer’s disease, a disease without a cure. Epidemiological studies that directly test associations between risk factors and Alzheimer’s disease are difficult to conduct because identified associations are in many cases confounded. The time period in which people are affected by risk factors may have ended years before clinical symptoms are observed.
This project will implement Mendelian randomization — using genetic instrumental variables to make inferences about causal effects based on observational data — to identify risk factors for Alzheimer’s. The project relies on integration with the Wisconsin Registry for Alzheimer’s Prevention.
The research is expected to produce an atlas of causal risk factors, including complex human traits, genes and their tissue-dependent transcriptional activities, serum and metabolites, for Alzheimer’s disease. These results can be used to guide future studies and therapeutics development. Methods developed in this project will be released as publicly accessible software packages.
Hyunseung Kang, Assistant Professor of Statistics
Qiongshi Lu, Assistant Professor of Biostatistics and Medical Informatics
Corinne Engleman, Associate Professor of Population Health Sciences
Funding: UW Data Sciences Initiative
Recent evidence suggests that microbial communities in human bodies (i.e. human microbiome), particularly those found in the intestine, play an essential role in inflammation and age-related conditions. However, most previous microbiome studies on aging have been characterized by small sample sizes and limited measurements of aging biomarkers/phenotypes. Moreover, there has been limited progress in the ability to analyze longitudinal microbiome data.
This project draws on the Wisconsin Longitudinal Study (WLS), a study of older adults who have been tracked since birth, and who, now in their late 70s, are beginning to experience rapid changes in aging and inflammatory related chronic disease burden.
The research team will develop and apply novel methods to characterize the variations of gut microbial composition with advancing age and age-related chronic inflammation and associated diseases. Deliverables from this project include a valuable dataset for microbiome research in aging, new methods and new knowledge of microbiome in aging process that will be described through peer-reviewed publications in statistics and medical science, and freely available software packages and tools for analyzing microbiome data.
ZhengZheng Tang, Assistant Professor of Biostatistics and Medical Informatics
Pamela Herd, Professor of Sociology
Federico Rey, Assistant Professor of Bacteriology
Jun Zhu, Professor of Statistics
Funding: UW Data Sciences Initiative