Connors-BRI Symposium

Incorporating Sex as Biologic Variable to Advance Health

May 24, 2021 | 3-5PM

Virtual Event

Rachel Soemedi, PhD

Brown University
Biomedical Informatics


Sex differences in human health and disease are common, but severely understudied. This gap of knowledge prevents accurate risk assessment and stratification for effective and safe therapeutic interventions for sex-biased diseases. Historically, females are more often disadvantaged from male-predominant clinical study participants. Recent re-analyses of previous genome-wide association studies (GWAS) uncovered many sex-specific and sex-asymmetric disease-associated loci that are widespread throughout the genome. This suggests that genetic landscapes that shape complex disease traits are sex divergent. Recent evidence also indicates thousands of genes being sex-differentially expressed, both quantitatively (expression level) and qualitatively (splicing patterns), and they exhibit significant tissue specificity. We hypothesize that sex divergent genomes are inherent in human populations and manifest as sex-asymmetric variant allele frequency and sex-biased disease-associated haplotypes. We investigate the characteristics of the sex-biased variants (SBV) in either allele frequency (freq-SBVs) and/or phenotypic association (phe-SBVs) in gnomAD, UK Biobank and Japan Biobank datasets. We found that freq-SBVs are highly shared between different populations and they are enriched in known tissue-specific sex-differentially expressed genes. The direction and magnitude of sex biased allele frequency of shared freq-SBVs are also significantly correlated between populations. The highly shared freq-SBVs are predominantly found in transcription factor binding sites (TFBS) that are known to regulate genes involved in embryonic developments, including heart morphogenesis, central nervous system and skeletal muscle tissue developments. They have primary biological roles in alternative splicing (different isoforms from a single gene) and major pathways involved in drug metabolisms, cardiovascular disorders, cancer, autoimmune and psychiatric diseases. Interestingly, ~10% of known disease variants that are present in gnomAD are freq-SBVs. We explore the various measures of freq-SBVs and phe-SBVs, and plan to validate freq/phe-SBVs in the transcriptomic levels at 50 different human tissues, by utilizing the allele-specific expression data from the GTEx consortium.


3PM – Welcome Remarks
3:05PM – Keynote Address
3:45PM – Featured Short Talks
4:20PM – Lightning Talks
4:50PM – Closing Remarks

Keynote Speaker

Janine Austin Clayton, MD

Janine Austin Clayton, M.D., Associate Director for Research on Women’s Health and Director of the Office of Research on Women’s Health (ORWH) at the National Institutes of Health (NIH), is the architect of the NIH policy requiring scientists to consider sex as a biological variable across the research spectrum. This policy is part of NIH’s initiative to enhance reproducibility through rigor and transparency. As co-chair of the NIH Working Group on Women in Biomedical Careers with NIH Director Dr. Francis Collins, Dr. Clayton also leads NIH’s efforts to advance women in science careers.

Prior to joining the ORWH, Dr. Clayton was the Deputy Clinical Director of the National Eye Institute (NEI) for seven years. A board-certified ophthalmologist, Dr. Clayton’s research interests include autoimmune ocular diseases and the role of sex and gender in health and disease. She is the author of more than 120 scientific publications, journal articles, and book chapters.
Dr. Clayton, a native Washingtonian, received her undergraduate degree with honors from Johns Hopkins University and her medical degree from Howard University College of Medicine. She completed a residency in ophthalmology at the Medical College of Virginia. Dr. Clayton completed fellowship training in cornea and external disease at the Wilmer Eye Institute at Johns Hopkins Hospital and in uveitis and ocular immunology at NEI.

Dr. Clayton has received numerous awards, including the Senior Achievement Award from the Board of Trustees of the American Academy of Ophthalmology in 2008 and the European Uveitis Patient Interest Association Clinical Uveitis Research Award in 2010. She was selected as a 2010 Silver Fellow by the Association for Research in Vision and Ophthalmology. In 2015, she was awarded the American Medical Women’s Association Lila A. Wallis Women’s Health Award and the Wenger Award for Excellence in Public Service. Dr. Clayton was granted the Bernadine Healy Award for Visionary Leadership in Women’s Health in 2016. She was also selected as an honoree for the Woman’s Day Red Dress Awards and the American Medical Association’s Dr. Nathan Davis Awards for Outstanding Government Service in 2017.