Genetic correlation found between abdominal fat and cardiovascular disease
UWA researcher Dr Gemma Cadby and colleagues at UWA and Curtin have shown for the first time that genes known to be associated with the cardiometabolic syndrome (CMS) may also be associated with central adiposity (abdominal fat), independent of obesity.
Overweightness and obesity affect more than two billion adults globally and are known to increase the chance of developing risk factors for CMS. Cardiovascular disease (CVD), a frequent outcome of CMS, is the leading cause of death worldwide. Susceptibility to CVD is known to have a significant genetic component, however, this is not yet well understood.
To better understand the heritability of complex diseases, such as CVD, and identify rare genetic variant risk factors, it is helpful to study data from large, densely affected families. However, suitable family studies are rare.
In a flagship project led by Professor Eric Moses, researchers at UWA, Curtin and the Centre for Genetic Origins of Health and Disease (GOHaD) have transformed the iconic Busselton Health Study into a unique Australian family dataset that can be used to investigate genetic risk factors for CVD and other complex diseases. This five-year project, the Busselton Family Heart Study, was awarded more than $2 million in grant funding from the NHMRC in 2016. The project aims to identify specific heritable genetic differences between individuals that put us at greater risk of CVD.
In their recent paper published in Human Genetics, the researchers describe how genetic data from 4671 Busselton Health Study participants was used to estimate family relationships and determine whether CMS and anthropometric traits share genetic risk factors (pleiotropy). Nine CMS traits were investigated, including triglycerides, cholesterol levels, insulin and glucose, as well as fifteen anthropometric traits, including BMI, weight, waist–height ratio, body part circumferences, and skinfold thickness.
This research has identified five statistically significant genetic correlations that represent traits associated with central adiposity (the accumulation of fat in the lower torso around the abdominal area). Central adiposity has been strongly linked to insulin resistance, type 2 diabetes, and cardiovascular disease genetic risk factors, and the new findings suggest that genes known to be associated with CMS are also associated with central adiposity (as opposed to overall adiposity, which is measured as BMI).
This analysis was limited to Busselton Health Study participants of European ancestry (Busselton is a semi-rural, historically stable community ~230 km south of Perth; predominantly of British Anglo-Saxon origin), therefore observed heritabilities and genetic correlations might not be generalisable to other populations. However, four of the five significant genetic correlations were validated in a study of Mexican–Americans, and the genetic correlations are expected to be consistent across other ethnicities.
Future research for the Busselton Family Heart Study project will seek to identify novel rare genetic risk variants for CVD by analysing the whole genome sequences of 1000 individuals within family groups from the Busselton Health Study, in conjunction with plasma lipidome measurements. Plasma lipid groups are heritable traits and are established major risk factors for CVD.
(Source: The University of Western Australia, Human Genetics)