Study sheds light on sex-based differences in gene regulation

New research from Harvard T.H. Chan School of Public Health and Brigham and Women’s Hospital has uncovered sex-based differences in networks that regulate gene expression in a large number of human tissues.

The finding is important because it can help explain sex-specific differences in disease risk, development, progression, and response to therapy, and could help guide therapeutic strategies in men and women, according to John Quackenbush, Henry Pickering Walcott Professor of Computational Biology and Bioinformatics, chair of the Department of Biostatistics, and co-corresponding author of the study.

The study was published June 23, 2020 in Cell Reports following a multidisciplinary team effort led by Dawn DeMeo of Brigham and Women’s Hospital and Quackenbush.

The research team modeled gene regulatory networks in 29 tissues, using data from nearly 500 participants in the Genotype-Tissue Expression (GTEx) project, according to Camila Lopes-Ramos, research scientist in the Department of Biostatistics and first author of the study. Analyzing the resulting set of almost 8,300 networks, the scientists found that, in most tissues, the network of factors that control gene expression differs between women and men. DeMeo noted that sex-based differences in gene regulation involve genes that play a role in diseases such as Parkinson’s, Alzheimer’s, diabetes, and cardiomyopathy.

Addressing the mechanisms of sex and gender differences will be essential for 21st century scientific and medical innovation, according to the authors. They wrote that the new findings “underline the importance of considering systems-level differences in gene regulation to understand how sex differences may contribute to health and disease.”

Read the study: Sex Differences in Gene Expression and Regulatory Networks across 29 Human Tissues

Read a GenomeWeb article about the study: Tissue Network Analysis Points to Significant Sex-Related Regulatory Differences