Genome-Wide Association Studies and Risk Scores for Coronary Artery Disease: Sex Biases

  • Sean G. ByarsEmail author
  • Mike Inouye
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1065)


Phenotypic sex differences in coronary artery disease (CAD) and its risk factors have been apparent for many decades in basic and clinical research; however, whether these are also present at the gene level and thus influence genome-wide association and genetic risk prediction studies has often been ignored. From fundamental and medical standpoints, this is critically important to assess in order to fully understand the underlying genetic architecture that predisposes to CAD and better predict disease outcomes based on the interaction between genes, sex effects, and environment. In this chapter we aimed to (1) integrate the history and latest research from genome-wide association studies for CAD and clinical and genetic risk scores for prediction of CAD, (2) highlight sex-specific differences in these areas of research, and (3) discuss reasons why sex differences have often not been considered and, where present, why sex differences exist at genetic and phenotypic levels and how important they are for consideration in future research. While we find interesting examples of sex differences in effects of genetic variants on CAD, genome-wide association and genetic risk studies have typically not tested for sex-specific effects despite mounting evidence from diverse fields that these are likely very important to consider at both the genetic and phenotypic levels. In-depth testing for sex effects in large-scale genome-wide association studies that include autosomal and often excluded sex chromosomes alongside parallel improvements in resolution of sex-specific differences for risk factors and disease outcomes for CAD has the potential to substantially improve clinical and genetic risk prediction studies. Developing sex-tailored genetic risk scores as has been done recently for other disorders might be also warranted for CAD. In the era of precision medicine, this level of accuracy is essential for such a common and costly disease.


GWAS Coronary risk factors Single nucleotide polymorphism Sex-specific analysis Genetic risk score Women’s Genome Health Study 



The Framingham Heart Study (FHS) dataset was obtained from dbGaP (phs000007), approved by the University of Melbourne Health Sciences Human Ethics Sub-Committee (HREC 1442186). The FHS is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University (Contract No. N01-HC-25195 and HHSN268201500001I). This chapter was not prepared in collaboration with investigators of the Framingham Heart Study and does not necessarily reflect the opinions or views of the Framingham Heart Study, Boston University, or NHLBI. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the chapter.


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Melbourne Integrative Genomics, School of BiosciencesThe University of MelbourneParkvilleAustralia
  2. 2.Department of PathologyThe University of MelbourneParkvilleAustralia
  3. 3.Systems Genomics LabBaker Heart and Diabetes InstituteMelbourneAustralia

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