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The association of the paraoxonase (PON1) Q192R polymorphism with depression in older women: findings from the British Women’s Heart and Health Study
  1. Debbie A Lawlor1,
  2. Ian N M Day2,
  3. Tom R Gaunt2,
  4. Lesley J Hinks2,
  5. Nick Timpson1,
  6. Shah Ebrahim3,
  7. George Davey Smith1
  1. 1Department of Social Medicine, University of Bristol, Bristol, UK
  2. 2Human Genetics Division, School of Medicine, University of Southampton School of Medicine, Southhampton, UK
  3. 3Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
  1. Correspondence to:
 Dr D A Lawlor
 Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol BS8 2PR, UK; d.a.lawlor{at}


Background: The association between the R allele of PON1 Q192R and symptoms reported by sheep dippers and Gulf War veterans has been used to suggest a biological basis for these symptoms. In the absence of such studies in non-occupational populations, these conclusions may not be valid.

Objective: To examine the association of paraoxonase (PON1) Q192R with a report of ever being diagnosed with depression among a random sample of 3266 British women, aged 60–79 years.

Results: The R allele of PON1 Q192R was associated with depression: per-allele odds ratio 1.22 (95% confidence interval: 1.05 to 1.41) in this population.

Conclusions: These findings suggest that the association of PON1 Q192R with symptoms of depression in occupationally exposed groups may be driven by exposure to toxins that everyone in the general population is exposed to rather than exposure to toxins specifically used by sheep dippers or Gulf War veterans, or that other mechanisms underlie the association. This is because the study population in which we have found an association consisted of British women aged 60–79 years, few of whom were sheep dippers or Gulf War veterans. When using genotype–outcome associations to infer causality with respect to an environmental exposure modified by the genotype, it is important to examine these associations in general populations and in those specifically exposed to the putative agent. The possible role of PON1 Q192R in psychiatric morbidity requires further examination.

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  • DAL and GDS developed the study aim and design. INMD, together with SE and DAL, obtained funding for the DNA bank and genotyping set-up. Genotyping assays were set up by TRG and LJH, under the supervision of INMD. NT contributed to the management of the genetic data. DAL undertook the initial analysis and coordinated writing of the paper. All authors contributed to the final version. DAL and INMD act as guarantors. The British Women’s Heart & Health Study is co-directed by Professor Peter Whincup and Dr Goya Wannamethee, in addition to two of the authors (SE and DAL).

  • Funding: The British Women’s Heart and Health Study is funded by the UK Department of Health and British Heart Foundation. DAL is funded by a UK Department of Health Career Scientist Award. NT is funded by a UK Medical Research Council studentship. TRG is funded by the UK Medical Research Council. The views expressed in this publication are those of the authors and not necessarily those of any of the funding bodies. The funding bodies have had no influence over the scientific work or its publication.

  • Competing interests: None.

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