European Journal of Human Genetics (2009) 17, 357–367; doi:10.1038/ejhg.2008.156; published online 17 September 2008

Lactase persistence-related genetic variant: population substructure and health outcomes

George Davey Smith1, Debbie A Lawlor1, Nic J Timpson1, Jamil Baban2, Matt Kiessling2, Ian N M Day1 and Shah Ebrahim3

  1. 1MRC Centre for Causal Analyses in Translational Epidemiology, Department of Social Medicine, University of Bristol, Bristol, UK
  2. 2Human Genetics Division, School of Medicine, University of Southampton School of Medicine, Southampton, UK
  3. 3Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK

Correspondence: Professor G Davey Smith, MRC Centre for Causal Analyses in Translational Epidemiology, Department of Social Medicine, University of Bristol, Bristol BS8 2PR, UK. Tel: +44 117 928 7329; Fax: +44 117 928 7325; E-mail:

Received 9 August 2007; Revised 9 July 2008; Accepted 16 July 2008; Published online 17 September 2008.



Lactase persistence is an autosomal-dominant trait that is common in European-derived populations. A basic tendency for lactase persistence to increase from the southeast to the northwest across European populations has been noted, but such trends within countries have not been extensively studied. We genotyped the C/T−13910 variant (rs4988235) that constitutes the putatively causal allele for lactase persistence (T allele representing persistence) in a general population sample of 3344 women aged 60–79 years from 23 towns across Britain. We found an overall frequency of 0.253 for the C (lactase non-persistence) allele, but with considerable gradients of decreasing frequency from the south to the north and from the east to the west of Britain for this allele. Daily sunlight was positively related to C (non-persistence) allele prevalence. However, sunlight exposure and latitude are strongly correlated, and it was not possible to identify which is the primary factor statistically underlying the distribution of lactase persistence. The C/T−13910 variant (rs4988235) was not related to drinking milk or bone health (although drinking milk itself was protective of bone health), and was essentially unrelated to a wide range of other lifestyle, health and demographic characteristics. One exception was general health being rated as being poor or fair, for which there was an odds ratio of 1.38 (1.04, 1.84) for women homozygous for the C allele; on adjustment for latitude and longitude of place of birth, this attenuated to 1.19 (0.87, 1.64). The lactase persistence variant could contribute to the examination of data for the existence of, and then statistical control for, population substructure in genetic association studies.


lactase persistence, British Women's Heart and Health Study, bone health, population stratification, milk



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