1. ¹Clinical and Molecular Genetics Unit, Institute of Child Health, University College London, England, UK
2. ²Avon Longitudinal Study of Parents and Children, Bristol University, England, UK
3. ³Department of Community Medicine and Rehabilitation, Social Medicine, Umeå University, Umeå, Sweden
4. ⁴Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
5. ⁵Demographic Database, Umeå University, Umeå, Sweden
6. ⁶Department of Biosciences, Preventive Nutrition Karolinska Institute, Karolinska, Sweden

Correspondence: Professor M Pembrey, Institute of Child Health, University College London, Picketts South, Picketts Lane, Salford, Redhill, Surrey RH1 5RG UK. Tel/fax: +44 1293 771202; E-mail: M.Pembrey@bristol.ac.uk

Received 10 June 2005; Revised 1 September 2005; Accepted 18 October 2005; Published online 14 December 2005.

Abstract

Transgenerational effects of maternal nutrition or other environmental 'exposures' are well recognised, but the possibility of exposure in the male influencing development and health in the next generation(s) is rarely considered. However, historical associations of longevity with paternal ancestors' food supply in the slow growth period (SGP) in mid childhood have been reported. Using the Avon Longitudinal Study of Parents and Children (ALSPAC), we identified 166 fathers who reported starting smoking before age 11 years and compared the growth of their offspring with those with a later paternal onset of smoking, after correcting for confounders. We analysed food supply effects on offspring and grandchild mortality risk ratios (RR) using 303 probands and their 1818 parents and grandparents from the 1890, 1905 and 1920 Överkalix cohorts, northern Sweden. After appropriate adjustment, early paternal smoking is associated with greater body mass index (BMI) at 9 years in sons, but not daughters. Sex-specific effects were also shown in the Överkalix data; paternal grandfather's food supply was only linked to the mortality RR of grandsons, while paternal grandmother's food supply was only associated with the granddaughters' mortality RR. These transgenerational effects were observed with exposure during the SGP (both grandparents) or fetal/infant life (grandmothers) but not during either grandparent's puberty. We conclude that sex-specific, male-line transgenerational responses exist in humans and hypothesise that these transmissions are mediated by the sex chromosomes, X and Y. Such responses add an entirely new dimension to the study of gene–environment interactions in development and health.