Informing women’s cardiovascular health through genomic analysis of extreme endurance athletes
2015 (English)Conference paper, Abstract (Refereed)
Cardiovascular health exists as a spectrum of wellness and disease states. We hypothesize that interrogating the tail ends of the distribution for individuals with extreme phenotypes, such as high VO2max in endurance athletes, will inform prevention, cause and treatment of pathogenic conditions. Mounting literature suggests that the physiological path to athletic performance is different among males and females. Traits with published sexual dichotomy include lactate threshold, efficiency, heat management, and fat metabolism. To define the genetic roots of this dichotomy, we propose to investigate sex-specific genetic determinants of VO2max among elite endurance athletes. We have recruited 36 female (VO2max>63 ml/kg; >99.99th percentile) and 129 male (>75 ml/kg) elite athletes (n=167) who have been consented and undergone enhanced whole exome sequencing. Even with differential eligibility, skewed recruitment (1:3.5) is a challenge. We will recruit a total of 100 female and 156 male elite athletes, and analyze these 256 exomes for burden of rare genetic variation that may impact sex-specific determinants of VO2max. We will combine these data with an additional 1850 samples of elite athletes to evaluate for common variants that have sex-specific effects on VO2max. Lastly, we will do a sex specific genetic cohort comparison of endurance athletes with existing collections of cardiovascular disease patients. Our preliminary results show tantalizing evidence for several highly plausible sex specific genes, including androgen receptor (AR) and FTO. The AR is the target of several known performance enhancing drugs, such as testosterone. FTO is associated with numerous aspects of body composition, energy management and even some evidence for age of menarche. While already promising, rigorous analysis, increased sample size and orthogonal replication is required as our next step.
Place, publisher, year, edition, pages
VO2max, Sex differences, Sports genetics
Medical Genetics Cardiac and Cardiovascular Systems Sport and Fitness Sciences
Research subject Medicine/Technology; Medicine/Technology
IdentifiersURN: urn:nbn:se:gih:diva-3963OAI: oai:DiVA.org:gih-3963DiVA: diva2:844415
OSSD (Organization for the Study of Sex Differences) Annual Meeting, Stanford, USA, April 21-23, 2015.
ProjectsELITE (Exercise at the Limit - Inherited Traits of Endurance)