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Original article
Age-related macular degeneration: the importance of family history as a risk factor
  1. Humma Shahid1,2,
  2. Jane C Khan1,3,
  3. Valentina Cipriani4,
  4. Tiina Sepp1,
  5. Baljinder K Matharu1,
  6. Catey Bunce4,
  7. Simon P Harding5,
  8. David G Clayton1,
  9. Anthony T Moore4,
  10. John R W Yates1,4,
  11. for the Genetic Factors in AMD Study Group*
  1. 1Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
  2. 2Oxford Eye Hospital, Oxford, UK
  3. 3Department of Ophthalmology, Royal Perth Hospital, Perth, Western Australia
  4. 4Institute of Ophthalmology, University College London and Moorfields Eye Hospital, London, UK
  5. 5Ophthalmology Research Unit, School of Clinical Sciences, University of Liverpool, Liverpool, UK
  1. Correspondence to Humma Shahid, Oxford Eye Hospital, West Wing, John Radcliffe Hospital, Headington, Oxford OX3 0LU, UK; hummashahid{at}


Background Family history is considered a risk factor for age-related macular degeneration (AMD). With the advent of effective therapy for the disease, the importance of family history merits further investigation. This study quantifies the risk associated with family history, first, by a case–control study of reported family history and, second, by examining the siblings of AMD cases.

Methods The authors recruited cases with advanced AMD, spouses and siblings. All subjects were carefully phenotyped. Clinical findings in the siblings were compared with spouses. Information about family history was collected. The ORs for reported family history of AMD were calculated. Analyses were adjusted for age, smoking and genotype.

Results 495 AMD cases, 259 spouses and 171 siblings were recruited. The OR for AMD was 27.8 (CI 3.8 to 203.0; p=0.001) with a reported family history of an affected parent and 12.0 (CI 3.7 to 38.6; p<0.0001) with a history of an affected sibling. ORs adjusted for age and smoking were higher. Examination of siblings confirmed their increased risk with 23% affected by AMD and an OR of 10.8 (4.5 to 25.8; p<0.0001). Adjusting for age increased the OR to 16.1 (6.2 to 41.8).

Conclusion The risk of AMD is greatly increased by having an affected first-degree relative. Those at risk need to be made aware of this and AMD patients should advise siblings and children to seek prompt ophthalmological advice if they develop visual symptoms of distortion or reduced vision.

  • Age-related macular degeneration
  • genetics
  • sibling
  • glaucoma
  • retina
  • macula
  • epidemiology
  • embryology and development
  • dystrophy
  • visual pathway
  • electrophysiology

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  • * Genetic Factors in AMD Study Group: S S Bhattacharya, P N Bishop, P Black, Z Butt, V Chong, N E Day, C Edelsten, A Fitt, D W Flanagan, A Glenn, C Jakeman, C Jones, R J Lamb, A Lotery, V Moffatt, C M Moorman, T Peto, R J Pushpanathan, E Redmond, T Rimmer and D A Thurlby.

  • Funding MRC programme grant (reference G0000067), 2001–2006, to fund salary and material support. This work has been supported by grants from the MRC, UK (JRWY, ATM, DGC) and the Macular Disease Society (JRWY, ATM). VC is funded by a grant from the Guide Dogs for the Blind Association. DGC is supported by the Wellcome Trust and the Juvenile Diabetes Research Foundation. This research has received a proportion of its funding from the Department of Health's NIHR Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital and UCL Institute of Ophthalmology. The views expressed in the publication are those of the authors and not necessarily those of the Department of Health.

  • Competing interests None.

  • Patient consent All patients involved in the study gave signed, informed consent to be enrolled. No patient is individually identified in this manuscript and the patients gave consent for results of the study to be published.

  • Ethics approval MREC and LREC.

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