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Multifactorial inheritance

Understand the concept of multi-factorial inheritance and how it applies to taking family histories.
In order for us to understand the importance and purpose of taking a family history, we must understand the concept of multi-factorial inheritance.

Many common chronic disorders follow this pattern of inheritance; Cancer and Cardio-vascular disease are key examples, others are Diabetes, Dementia, Asthma, Inflammatory Bowel Disease, the list goes on.

Cancer in the family: importance? Arrow from environmental factors: nurture 80-85%; polygenic: likely contribution of several genes each with individually small effect, but greater when acting in combination with each other and the environment 10-15%; to genetic factors: nature Autosomally inherited or single gene condition 3-5%Click to expand

All cases of a particular multi-factorial disease will lie on a spectrum; at one end cases are caused virtually solely by environmental factors, at one end, to virtually solely by genetic factors at the other. We can all bring to mind examples of cancers with underlying environmental causal factors: lung cancer and smoking, cervical cancer and HPV. At the other end of the spectrum around 3-5% of all diagnoses result from an underlying autosomal genetic condition (one that is not sex-linked): examples include breast cancer and BRCA1 or BRCA2 genes, colo-rectal cancer and the APC gene, giving rise to Familial Adenomatous Polyposis.

A further 10-15% of all diagnoses of a multi-factorial condition are likely to have a mixed aetiology. These patients have been recognised to have an increased risk through epidemiological studies of families with relevant family histories. It is now thought likely that the increased risk results from the effects of multiple genes each individually contributing a small increase in risk, and their interaction with environmental factors. This is known as polygenic risk.

Therefore 80-85% of patients will not have an increased risk of developing a condition over and above the general population: these patients fall into the ‘near-population’ risk group.

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Genomic Scenarios in Primary Care

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