NIH ORWH GWAS, Sex and Chromosomes Think Tank

Date and Time

– February 27, 2019, 05:00 PM EST
Event Information

ORWH is hosting this virtual think tank to identify gaps related to the consideration of sex as a biological variable (SABV) in genome-wide association studies (GWAS).

The meeting’s organizers are specifically interested in answering the following questions:

  1. To what extent are sex chromosomes ignored or underrepresented in GWA studies, and what are the underlying biological, methodological, technical, and cultural factors responsible for this?
  2. What biologically significant information is lost in GWA studies when investigators control for sex (e.g., by regressing sex effects out of their analyses) but do not analyze for sex (e.g., by performing sex-stratified analyses across the autosomal genome)?
  3. What solutions can help improve the analysis of sex chromosomes and the consideration of SABV in GWA studies, as well as the reporting of sex effects and results stratified by sex?
  4. To what extent can historical GWAS datasets be re-examined to achieve a more thorough consideration of the sex chromosomes and SABV using already-published data? What challenges are associated with tapping into such data to advance the foundation of genetic research for improved gender-based medicine?
  5. How should additional individual medical information (e.g., pubertal/menopausal, endocrinological, hormonal, and reproductive trait data) or other information about specific traits (e.g., results of GWAS meta-analyses) be incorporated into the research to help interpret and refine disease GWA studies?

Contact if you have any questions.


Sex is the single largest risk factor for many diseases and conditions, and strong influences of sex are known across all medical disciplines. Sex influences can manifest as biases in disease prevalence between the sexes (e.g., 90% of lupus patients are women), as differences in trait means between the sexes (e.g., fat distribution varies between sexes), or even as discrete, non-overlapping sexual dimorphisms in form and function. Most of these sex influences have a strong genetic basis, but linkage, GWAS, and heritability studies have failed to identify the majority of variance explained by the sex chromosomes, including many of their constituent genes. 

While many such studies have ignored the sex chromosomes for technical reasons, enough of them have demonstrated an underestimation of sex chromosome effects or a neglect of SABV in genetic research for other reasons. The underlying explanations may be subtle and complex, and they are certainly worthy of study both for the basic mechanistic insights into sex differences and for a better understanding of pathophysiology.