Mom and Dad not equally to blame for some bad genes

Depending which parent passes on a trait, disease risk could go up or down

Great. Just in time for the holidays, researchers are fueling the debate about which side of the family is responsible for your more undesirable traits.

Genetic variations can either contribute to disease risk, or help protect against disease, depending on which parent passes along the variant, researchers at deCODE genetics in Iceland and colleagues report in the Dec. 17 Nature. The team uncovered common single-letter genetic changes — called SNPs, short for single nucleotide polymorphisms — that were associated with diseases only when the change was inherited from a particular parent.

For instance, when inherited from the father, a SNP associated with breast cancer increases the risk of developing the disease. If passed down from the mother, this same SNP helps protect against breast cancer.

Which parent passes on a variation is also important for determining genetic predisposition for a type of skin cancer called basal cell carcinoma — the variant increases risk of skin cancer more when inherited from the father.

And three different SNPs affect risk for developing Type 2 diabetes depending on which parent passes the spelling change along, the team found. Two of the three diabetes-associated SNPs led to greater disease risk when inherited from the mother. The third decreased the risk of Type 2 diabetes when maternally inherited, but raised the chance of disease when paternally inherited.

Most large studies that search for genetic contributions to disease risk would miss such associations, says Aravinda Chakravarti, a geneticist at Johns Hopkins University who was not involved in the study. Current methods for calculating heritability of a disease assume that the effect of any one genetic variation is the same for everybody. This study shows at least one way genetic variations can affect people differently, he says.

Many diseases are known to run in families, but it has been very difficult to account for all of the genetic factors that are inherited. Most of the SNPs associated with disease account for only a small part of the genetic risk. The newly described “parent-of-origin effect” may help scientists find some of the missing risk factors, Chakravarti says.

Only deCODE genetics could have done such a study, Chakravarti says. The company has a large database of thousands of Icelandic participants. The database includes genetic information as well as family and medical histories. Knowing the genetic makeup of entire families is important for teasing apart maternal and paternal genetic influences, says Kari Stefansson, the company’s chief executive.

All of the disease-associated variants found in the study are located in the neighborhood of imprinted genes. Imprinting is a process that tags genes from one parent with chemical marks so that only the copy inherited from the other parent is turned on. The researchers purposely looked for SNPs near imprinted genes, hoping to find variants that act differently when inherited from the mother versus the father.

“This doesn’t come as an entire surprise, but no one has shown any molecular evidence” that disease risk could be inherited differently from each parent, Stefansson says.

Exactly how a single genetic variation can have two different effects is not known, but the new study shows that imprinting may affect gene activity close to the SNPs. That could mean that imprinting is more common than scientists previously believed or that there are other mechanisms for creating different outcomes from the same genetic code, says Chakravarti.

For now, the study doesn’t have any direct clinical impact, but it may contribute to improved risk calculations in the future and could point out previously overlooked contributions to disease, Stefansson says.

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