Genetics and stem cells

Parental DNA and disease risk

Researchers have found the clues to “the mother and father of all genetic mysteries”, according to The Times. The newspaper says it is not just the pattern of DNA that can affect different risks of a disease, but also which parent has passed these genes on to their offspring.

The complex genetic study behind this story has identified five variants in the DNA sequence that lie in close proximity to parent-specific genes which have been determined by only one parent. One of these five DNA variants was shown to affect the risk of type 2 diabetes, increasing risk when inherited from the father and reducing risk if inherited from the mother.

It is possible that it is not just the sequence of someone’s DNA that matters, but also the parent from which the sequence comes. However, it is important to consider these results in context, particularly with the risk of a disease such as type 2 diabetes, which has many links with lifestyle. Also, inheritance is complex, and a number of other genes may also be associated with disease risk.

Where did the story come from?

Augustine Kong and colleagues of the deCODE genetics group Landspitali-University Hospital, Reykjavik, Iceland, and the University of Cambridge carried out this research. The research was partly funded by a grant to decode the genetics of cancer issued by the European Union’s Seventh Framework Programme for scientific research. The study was published in the peer-reviewed scientific journal, Nature.

What kind of research was this?

This was a genome-wide association study investigating how hereditary susceptibility to disease may differ depending on which parent a particular genetic variant was inherited from.

Previous studies have frequently examined how possessing a particular DNA sequence may influence a certain human trait. But some claim that the research has overlooked the impact of each individual parent in providing this section of DNA.

The newspapers have accurately reflected the findings of this current research.

What did the research involve?

The researchers examined the DNA sequences of 38,167 people from Iceland, specifically looking for variant sequences of DNA (SNPs) that were associated with disease (i.e. were more common in people with a particular disease). The study population involved people with breast cancer (1,803 cases), basal cell type of skin cancer (1,181 cases), prostate cancer (1,682 cases) and type 2 diabetes (796 cases). The remainder of the study group comprised of healthy recruits without disease.

Genetic studies generally look at the prevalence of particular SNPs, but in this study the researchers wanted to focus on whether SNPs inherited from different parents had different effects. To explore this theory, the researchers focused on SNPs that were in proximity to known ‘imprinted’ genes, i.e. parent-specific genes which have been determined by only one parent. Previous research has so far identified only a small number of these imprinted genes in humans.

There were seven relevant SNPs to examine. The researchers used complex methods to identify which parent had provided the SNPs. They found that five of these seven had different effects depending on which parent they were inherited from. Previous research has identified that of the five SNPs identified, one was associated with breast cancer, one with basal cell skin cancer, and three with type 2 diabetes.

What were the basic results?

The researchers selected seven SNP variants on the basis that they were close to clusters of imprinted genes located in regions of chromosomes 11 and 7. For five of these seven SNP variants the sex of the parent providing the genes was estimated to affect the offspring’s likelihood of disease. For the two SNPs that have been linked to prostate cancer and coronary heart disease, it did not appear to matter which parent provided the variant.

The strongest link with parental origin was between one particular SNP on chromosome 11 and the risk for type 2 diabetes. The research found that, compared to the general disease risk in any person,  this variant increased the likelihood of type 2 diabetes by more than 1.2 times when inherited from the father, but reduced the likelihood to about 0.8 (i.e. is protective) when inherited from the mother.

How did the researchers interpret the results?

The researchers say that so far, previous genome-wide association studies have identified sequence variants that explain only a small part of the inherited nature of most human traits. They say that their results demonstrate that some of the remaining ‘obscure hereditability’ behind most traits may be hidden in more complex relationships involving certain sequence variants, some of which may be common but have little effect, others which may be rare but have a stronger influence on human traits.


This complex study has identified a number of DNA sequence variants that are in close proximity to ‘imprinted genes’ (parent-specific genes whose expression is determined - unusually - by one parent rather than both parents) which are known to affect the risk of certain diseases.

One of these five DNA variants affects the risk of type 2 diabetes, increasing risk of the disease when inherited from the father, and reducing risk if inherited from the mother. As Kári Stefánsson, chief executive of the study says, the research suggests that it may not be just the DNA sequence that matters, but also the parent from which the sequence comes.

The findings shed new light on the complex link between genetics and disease risk, but the findings may still not explain the entire picture:

  • Although the five DNA sequence variants (SNPs) examined were in close proximity to the imprinted genes, there is still the chance that these variants may play no role in the way the gene is expressed.
  • As the researchers say, there is the possibility of some small error when using their methods to assign which parent the SNP was inherited from.
  • There are likely to be numerous genes affecting disease risk, including other imprinted genes that have not yet been identified.
  • A person’s risk of disease is not determined by genetics alone. For example, being overweight or obese is the most important risk factor for type 2 diabetes.

At the current time, these research findings into the complexities of genetic inheritance have limited implication for disease prevention or treatment.

NHS Attribution