Family history of disease may be as much the result of shared lifestyle and surroundings as inherited genes, research has shown.
Factors that are common to the family environment – such as shared living space and common eating habits – can make a major contribution to a person’s risk of disease, the study found.
A study of common diseases in families across the UK has highlighted the importance of such factors in estimating a person’s risk for diseases such as high blood pressure, heart disease and depression.
Previous studies have identified genes that are linked to numerous medical conditions, yet these only account for part of a person’s likelihood of developing disease.
Researchers led by the University of Edinburgh’s Roslin Institute and MRC Human Genetics Unit examined the medical histories of more than 500,000 people and their families – including both blood and adoptive relatives.
They looked at incidences of 12 common diseases including high blood pressure, heart disease, and several cancers and neurological diseases.
By not accounting for shared environmental factors, scientists may overestimate the importance of genetic variation by an average of 47 per cent, the study found.
Experts say their findings will help to provide realistic expectations of the value of genetic testing for identifying people at risk of disease.
The research also underlines the need to identify environmental factors that contribute to diseases and how to modify them to reduce disease risk.
The study published in Nature Genetics, used data from the UK Biobank, a UK database of volunteers’ health.
Professor Chris Haley, of the University’s MRC Human Genetics Unit, said: “The huge UK Biobank study allowed us to obtain very precise estimates of the role of genetics in these important diseases. It also identified those diseases where the shared family environment is important, such as heart disease, hypertension and depression, and also equally interestingly those where family environment is of limited or no apparent importance, such as dementia, stroke and Parkinson’s disease.”
The study was supported by the Biotechnology and Biological Sciences Research Council and the Medical Research Council, which provide strategic funding to The Roslin Institute and the Human Genetics Unit, respectively.
Cancer is a disease of the genome, involving widespread disruptions (mutations) to human DNA accumulating as the cells within a tumour evolve. These mutations have been studied for many years to provide insights into how tumours occur and progress. However up until recently technological and financial limitations meant that it was only possible to examine the DNA within genes, encompassing only around 3% of the total genome sequence. The other 97% of the genome is not well studied, but recent whole genome sequencing (WGS) datasets have emerged worldwide, based upon sequencing hundreds or thousands of tumours from cancer patients.
Researchers at the MRC Human Genetics Unit led by Professor Colin Semple have just published one of the largest studies of tumour WGS so far, including 11 different cancer types (Kaiser et al, 2016, PLOS Genet 12:(8):e1006207). They studied the patterns of mutations accumulating across cancer genomes using carefully controlled comparisons in a novel computational analysis, paying close attention to functional regulatory sites. These sites are short DNA segments that act as molecular switches, and are known to turn the expression of genes on or off in a variety of human cell types.
They discovered strikingly high rates of mutation at functional regulatory sites across different cancers, relative to matched control sequences. This excess of mutations is predicted to disrupts the binding sites of most known transcription factors, which bind to these sites and activate genes. Particular factors, such as CTCF, suffer unusually high loads of mutation suggesting widespread impacts on the physical organisation of chromosomes. These unusual patterns could conceivably be generated by selection during tumour evolution, as the tumour cells adapt to invade normal tissue more effectively.
However, Kaiser et al show that the patterns are likely to simply reflect mutational bias, with functional regulatory sites being inherently prone to accumulating large numbers of mutations. Why this bias should exist remains mysterious, and is the focus of ongoing work.
The study suggests that tumours accidentally but unavoidably alter the regulation of many, and perhaps most, human genes as they develop over time. Understanding this progression better may allow us to develop new approaches to detecting earlier and later stages of cancers. The work was made possible by core MRC funding to Semple and his colleagues.