Genetic disorders and their transmission are frightening and complex topics. One of my greatest fears is passing Crohn’s or ulcerative colitis onto my future children. A recent study sheds new light on the way genetics influence disease risk.

Science is progressing our understanding of the human genome in leaps and bounds. A new study conducted by MIT and Harvard helps shed new light on why not everyone carrying a high-risk gene will necessarily develop a disease.

Genetic disorders and risk scores

Often someone is considered genetically predisposed to a disease if they carry a single, specific gene related to the condition.

For example, cancer runs in many families. Angelina Jolie is perhaps the highest profile of this type of case. After discovering she carried the faulty gene BRCA1, she chose to undergo a preventative double mastectomy. Her mother had died of breast cancer at age 56 and Jolie took action to avoid the same fate.

Woman in hospital. Photo credit: Pixabay

However, among carriers of this gene, the likelihood of actually getting the disease has proven hard to predict.

The recent research used genome-wide risk scores which look beyond the ‘bad’ gene to take into account multiple genetic factors. Known as polygenic scores, these were used to distinguish between people carrying a single faulty gene. Published in Nature Communications, the results show a range of disease predictability based on polygenic scores. This has both biological and clinical implications.

Distinguishing genetic disorder risks

The study used clinical data from over 80,000 people. Co-lead author Akl Fahed explained how we “often assume that having a high-risk variant makes eventually getting the disease all but inevitable,” but in contrast to this, “an important subset actually go on to live their lives normally.”

For someone with Jolie’s breast cancer gene, the risk of developing cancer ranged from 13% to 76% depending on their polygenic score.

Testing a gene linked to colorectal cancer, the risk gradient varied from 11% to 80%. And with heart disease, someone with a high-risk gene could have a chance as low as 17% of developing the condition. That’s not too dissimilar to the population average. However, a high-risk gene combined with a high polygenic score presents a 78% disease probability.

DNA strands and microbes. Photo credit: Pixabay

Important life choices

The study proposes a better approach to assessing disease risk in the future. A preventative procedure such as mastectomy or colon removal constitutes a major life decision. Knowing where you fit on the polygenic score spectrum could be a huge factor when choosing whether to undergo surgery. 

Senior author Amit Khera, leading physician-scientist at Massachusetts General Hospital, said, “We are thrilled to be able to offer state-of-the-art genetic risk assessment to our patients in the coming months. One of our next steps is to educate doctors and patients on more advanced types of genetic risk predictors, such as polygenic scores.”

This medical breakthrough came too late for me to live without an ostomy bag. But with no colon, and soon no rectum either, my colorectal cancer risk will be eliminated. For Angelina Jolie, her mastectomy prevents her following the tragic, untimely fate of her mother.

Future generations will benefit from a more thorough evaluation of genetic disorder risk. Hopefully, surgery can soon be avoided in all but the most necessary of cases.

Related Topics