New Genetic Links Identified for Heart Disease Risk Factors

Genetics have been implicated in cardiovascular and blood diseases for some time, however as these are complex diseases, it is extremely difficult to find specific genetic causes, but large scale genomic datasets can be used to help identify potential novel biological targets for studying cardiovascular and other diseases.

Two previous large-scale projects have provided the whole genome sequences needed: the UK10K project - a study of the genetic code of 10,000 people that aims to better understand links between rare genetic variations and disease; and the 1000 genome project. From this data, the scientists created a resource called a dense imputation panel, which is freely accessible to the scientific community.

A large team of international scientists led by those at the Welcome Trust Sanger Institute (Hinxton, UK) studied the genomes of almost 36,000 healthy people with European ancestry, looking for rare genetic links to known risk factors for disease, followed by association analysis with 20 quantitative cardiometabolic and hematological traits, such as raised levels of cholesterol or hemoglobin in the blood. The level of detail the imputation panel provides enabled the scientists to look at specific disease risk factors, and find 17 new genetic variants. Of these, 16 would have been extremely difficult to find without the imputation panel data.

The team reported 17 new associations, including six rare minor allele frequency (MAF) of less than 1% or low-frequency (1% < MAF < 5%) variants with platelet count (PLT), red blood cell indices, mean cell hemoglobin (MCH) and mean cell volume (MCV) and high-density lipoproteins (HDL) cholesterol. Applying fine-mapping analysis to 233 known and new loci associated with the 20 traits, they resolved the associations of 59 loci to credible sets of 20 or fewer variants and describe trait enrichments within regions of predicted regulatory function.

Valentina Iotchkova, PhD, the first author of the study, said, “This is the first stage of a discovery process that is going to tell us more about the contribution genetics makes to complex human diseases. We looked at where in the genome these 17 new variants lie to see what that could tell us about biology; about the changes they make to the body and how that could make a person more or less susceptible to disease..” The study was published September 26, 2016, in the journal Nature Genetics (www.nature.com).

Related Links:
Welcome Trust Sanger Institute