Gene Discovered for Congenital Heart Disease

An international team of scientists, led by those at the University of Manchester (Greater Manchester, UK) and Newcastle University (Newcastle upon Tyne, UK) conducted a genome-wide study of over 2,000 CHD patients and measured over 500,000 genetic markers, which vary in the general population. The genetic markers in the patients were compared to the markers of over 5,600 people in good health who acted as a control group.

The scientists found a relationship between a particular region of the human genome and risk of atrial septal defect (ASD), which is a form of congenital heart defect that enables blood flow between two compartments of the heart called the left and right atria. The investigators went on to confirm their findings in additional cases of atrial septal defect and healthy controls.

When all CHD phenotypes were considered together, no region achieved genome-wide significant association. However, a region on chromosome 4p16, adjacent to the muscle-segment homeobox 1 (MSX1) and syntaxin 18 (STX18) genes, was associated with the risk of ostium secundum atrial septal defect in the 340 cases in the discovery cohort, and this association was replicated in a further 417 ASD cases and 2,520 controls.

Bernard Keavney, MD, professor of cardiology and senior author of the study, said, “Identifying a gene associated with one type of CHD was an important step forward. We found that a common genetic variation near a gene called MSX1 was strongly associated with the risk of a particular type of CHD called atrial septal defect or hole in the heart. ASD is one of the most common forms of congenital heart disease, and it carries a risk of heart failure and stroke. We estimated that around 10% of ASDs may be due to the gene we found. We can now work to find out how MSX1 and/or its neighbor genes affect the risk of ASD." The study was published on May 26, 2013, in the journal Nature Genetics.

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University of Manchester

Newcastle University