Feature Christmas 2017

The Christmas gift of genetic uncertainty

BMJ 2017; 359 doi: https://doi.org/10.1136/bmj.j5762 (Published 22 December 2017) Cite this as: BMJ 2017;359:j5762
  1. Christopher Semsarian, professor123,
  2. Ray Moynihan, senior research fellow45
  1. 1Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Sydney, NSW 2042, Australia
  2. 2Central Clinical School, Sydney Medical School, University of Sydney, Australia
  3. 3Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia
  4. 4Centre for Research in Evidence Based Practice, Bond University, Queensland, Australia
  5. 5Sydney Medical School—Public Health, University of Sydney, Sydney, Australia
  1. Correspondence to: C Semsarian c.semsarian{at}centenary.org.au

John is a 32 year old father of two who had been troubled by excess earwax since childhood. Turning to “Dr Google” he thought that his type of earwax might be the result of a genetic change (single nucleotide polymorphism; SNP) in the ABCC11 gene, which can lead to either “dry earwax” or “wet earwax.” Having annoyed his family for many years, John’s father gave him a direct to consumer, ancestry based genetic test kit as a Christmas gift a couple of years ago; for fairness, he gave the same gift to his adult daughter, Rebecca.

Although this genetic gift was focused on providing information specifically about family and ethnic origins, John discovered that this genetic information—comprising thousands of SNPs across the genome—could also be uploaded to a free website to identify the genetic risk of many human diseases, including earwax type. John and Rebecca each spat in the provided tubes and sent their samples off for genetic analysis. John received the genetic information regarding his ethnic origin, uploaded it, and received his “genetic report.” Most importantly for John, he finally discovered that he carried the C variant in the ABCC11 gene that causes wet earwax. But as he scrolled through the other genetic information, he was surprised to find that he carried genetic risk alleles for prostate cancer and early Alzheimer’s disease, and one that can lead to cardiomyopathy and sudden death in some people.

Rapid advances in genetic technologies have led to greater availability of genetic tests, ranging from online direct to consumer DNA test kits to clinical whole genome sequencing of all 22 000 human genes.1 Genetic testing can have clear benefits in terms of diagnosis and in guiding treatment strategies for the limited set of circumstances where interventions are proven to improve patient outcomes.2 But conducting comprehensive genetic investigations in people who are well and asymptomatic could do more harm than good and waste scarce resources. Whole genome sequencing can lead to the identification of up to 12 clinically actionable variants in well people,3 leading to extensive clinical investigations and unnecessary anxiety. Furthermore, many variants of uncertain significance are discovered. This is complicated further by “incidental findings,” whereby a genetic result unrelated to the patient’s primary disease is identified—for example, an epilepsy gene variant is found in a patient with cardiovascular disease.

These genetic changes, for which the gene function is either unknown or there is no available treatment or prevention, are a perfect storm for overdiagnosis and overtreatment.4 As Wilson and colleagues recently argued in their call for rigorous evidence based evaluation of genetic technologies, “The allure of a new understanding of biology cannot be sufficient to exempt genome based precision medicine from social requirements for evidence.”4 In those limited circumstances where benefit has been proven, or rigorous research is being conducted, providing people with appropriate education and counselling about the genetic testing process and potential outcomes, including benefits and harms and the uncertainties around them, is essential to ensure truly informed consent before any proposed genetic investigation.

John spent the next year satisfied with the knowledge of his earwax type but worried about his other genetic findings. He underwent a range of investigations including PSA screening, cognitive testing, and cardiac electrocardiography and echocardiography. His two young children also had cardiac screening because of the autosomal dominant inheritance pattern of the genetic variant for cardiomyopathy. All clinical tests were “negative,” but his worries about himself and his children continued despite the absence of any symptoms. At their next Christmas gathering, John compared his genetic ancestry results with Rebecca and found that they had different genetic origins. The discussions at the family Christmas dinner were interesting.


  • Competing interests: We have read and understood BMJ policy on declaration of interests and declare the following interests: none.

  • Provenance and peer review: Not commissioned; not externally peer reviewed.

  • CS is the recipient of a National Health and Medical Research Council (NHMRC) Practitioner Fellowship (#1059156). RM is the recipient of an NHMRC Early Career Fellowship. (#1124207)

  • Patients were not involved in the making of this article, and the characters are fictitious.


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