Article Text

Download PDFPDF

Pathogenic variants in the healthy elderly: unique ethical and practical challenges
  1. Paul Lacaze1,
  2. Joanne Ryan1,
  3. Robyn Woods1,
  4. Ingrid Winship2,3,
  5. John McNeil1
  1. 1 Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, ASPREE - Monash University, Melbourne, Victoria, Australia
  2. 2 Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Melbourne, Victoria, Australia
  3. 3 Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia
  1. Correspondence to Dr Paul Lacaze, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, The Alfred Centre, 99 Commercial Road, Melbourne, VIC 3004, Australia; paul.lacaze{at}


Genetic research into ageing, longevity and late-onset disease is becoming increasingly common. Yet, there is a paucity of knowledge related to clinical actionability and the return of pathogenic variants to otherwise healthy elderly individuals. Whether or not genetic research in the elderly should be managed differently from standard practices adapted for younger populations has not yet been defined. In this article, we provide an overview of ethical and practical challenges in preparing for a genetic study of over 14 000 healthy Australians aged 70 years or older enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) Healthy Ageing Biobank. At the time of consent, all participants in this study were free of life-threatening illness, cardiovascular disease or cognitive impairment. ASPREE is thus a cohort of healthy elderly individuals with seemingly minimal burden of genetic disease recruited without ascertainment bias. The cohort presents a unique opportunity to address the penetrance of known pathogenic variants in a population without disease symptoms; however, it also raises a number of ethical concerns regarding the interpretation and disclosure of variants with known clinical actionability. Some of the challenges include (a) how to manage the interpretation, disclosure and actioning of pathogenic variants found in otherwise healthy elderly adults without disease symptoms, (b) whether or not to disclose findings for the benefit of family members rather than elderly consented donors themselves, (c) how to manage the return of genetic findings to the elderly individuals who are now in severe cognitive decline or terminal illness, (d) how to ensure quality of information and clinical service upon disclosure of results to this demographic and (e) how to prepare for the insurance implications of disclosing genetic information under Australian law. We discuss these and other dilemmas and propose a defensible plan of management.

Trial registration number ISRCTN83772183

  • Genetic Counselling/Prenatal Diagnosis
  • Genetic Information
  • Genethics
  • Genetic Screening/Testing
  • Elderly and Terminally Ill

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:

Statistics from


  • Twitter Follow Paul Lacaze @PaulLacaze

  • Contributors PL wrote the manuscript and provided the intellectual conception of the article. RW and JM made substantial contributions to the conception and design of the work. JR and IW were critical in providing intellectual input and drafting and revising the article.

  • Competing interests None declared.

  • Ethics approval The Alfred Hospital Office of Ethics and Research Governance.

  • Provenance and peer review Commissioned; externally peer reviewed.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Other content recommended for you