Connors-BRI Symposium

Incorporating Sex as Biologic Variable to Advance Health

May 24, 2021 | 3-5PM

Virtual Event

Joanna Lin

Bowdoin College


Epidemiological research has uncovered multiple risk factors for COVID-19 severity, including sex, metabolic conditions such as type 2 diabetes and obesity, and social determinants of health. Meanwhile, genetic studies have shown that specific genomic regions are associated with severe COVID-19. However, it is not clear whether genetic factors impact the relationship between these key risk factors and COVID-19 severity. We sought to understand the interactions between genetic variants and risk factors in order to shed light on COVID-19 biology and susceptible individuals. We undertook a series of three genome-wide gene-environment interaction studies in the UK Biobank, while conducting both interaction effect tests and joint tests of genetic main and interaction effects. The “environmental” exposures included sex, cardiometabolic conditions (obesity and type 2 diabetes status), and social determinants of health (as quantified by the multiple deprivation index), while the binary outcome was severe COVID-19, as defined by hospitalization or death due to COVID-19, while using the rest of the population as controls. We found five significant genomic regions (p<5e-8) that uncover some biological underpinnings of variable COVID-19 severity, two of which came from the sex joint analysis. One genome-wide significant variant (rs2268616, OR=1.6, 95% CI: 1.38-1.94), identified in the sex joint and cardiometabolic joint analyses, has been previously linked to testosterone levels and affects the expression of EIF2B2, which regulates viral mRNA translation. Interestingly, other studies have found that SARS-CoV-2 can enter the testis and delay viral RNA clearance in males, possibly contributing to differential immune responses between sexes. While we did not find substantial evidence for genetic modification of the importance of risk factors (via the interaction test), our joint test results showed that incorporation of these risk factors, particularly sex, improved the detection of genetic loci impacting COVID-19 severity.


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.