Elucidating the phenome-wide impact of sex and gender on disease

Project: Research project

Project Details

Description

The central goal of this proposal is to understand the role of sex in the comorbidity between depression and cardiovascular disease at both the epidemiological and molecular levels by employing quantitative genetic approaches to large-scale data. Dr. Barbara Stranger, Ph.D., is Co-Principal Investigator of this Multi-PI proposal. She is an Associate Professor of Pharmacology in the Department of Pharmacology, and core member of the Center for Genetic Medicine at Northwestern Feinberg School of Medicine. She will be responsible for analytic and computational aspects of integrating statistical genetics and functional genomics and will build sex-adjusted models of cardiovascular disease risk that include risk conferred by major depression. Dr. Stranger is a world’s expert on genetics of gene expression and the role of sex in the genetics of complex traits, with multiple publications in Nature, Science, and other journals on these topics. She was a member of the International HapMap Project and spent five years of her postdoctoral training at the Wellcome Trust Sanger Institute. Dr. Stranger was a funded member of the Analysis team of the NIH Genome Tissue Expression data (GTEx) Project, collaborates with Dr. Nancy Cox on analysis of these data, and is Chair of the Biological Sex group of the GTEx Analysis working group. Furthermore, she has regular interactions and collaborations with colleagues Dr. Stephen Montgomery, Dr. Alexis Battle, Dr. Tuuli Lappalainen, Dr. Haky Im, and Dr. Barbara Engelhardt, who are all highly-active investigators in the field of human regulatory variation in the context of health and disease. Dr. Stranger and Dr. Davis co-Chair the Sex-Specific Cross-Disorder working group of the Psychiatric Genomics Consortium, have published together on these topics, jointly mentored trainees, and organized symposia on sex differences at the previous two meetings of the World Congress of Psychiatric Genetics. Dr. Stranger is currently funded by an NCI R01 award to study the role of sex in the genetics and genomics of cancer and response to treatment. Dr. Stranger’s effort will be 20% in years 1-4 of the grant. Throughout the project, Dr. Stranger and her team will work closely with Dr. Davis and her team to optimally integrate analysis of sex differences in the genetics of coronary artery disease, major depression, and their associated laboratory tests with evidence of sex-specific functional variation, including sex-biased gene expression, allele-specific expression, and expression quantitative trait loci (eQTL). Her expertise in statistical genetics and genomics will ensure that state-of-the-art approaches are implemented to provide a balance between scientific rigor, power, and feasibility. Jointly with Dr. Davis’s team, she will apply known and novel techniques to build sex-adjusted models of cardiovascular disease risk that include risk conferred by major depression and genetic risk for major depression. Given Dr. Stranger’s prominent role as a funded member in the GTEx consortium and leader of the GTEx Biological Sex working group, she will harness those and other data to better understand the interplay between sex, depression, and cardiovascular disease. Her expertise in understanding the role of sex in the genetics and genomics of complex traits is extremely relevant for this study, as many aspects of these traits exhibit sex-differences. Throughout the study, Dr. Stranger will be in constant communication with Dr. Davis and her laboratory to guarantee application of the newest methods to analyze large-scale geneti
StatusFinished
Effective start/end date9/21/216/30/22

Funding

  • Vanderbilt University Medical Center (VUMC95892//1R01HG011405-01A1)
  • National Human Genome Research Institute (VUMC95892//1R01HG011405-01A1)

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