Multigenerational cohorts in patients with asthma and allergy

Abstract

Recent observations that disease risk can be transmitted across generations without the need for direct exposure of the child to the index environmental insult has sparked interest in transgenerational inheritance. Epigenetics describes processes that modify gene expression without a change in the nucleotide sequence. Epigenetic processes can be induced in response to environmental exposures, can influence disease risk, and might explain these multigenerational effects. In experimental models a number of epigenetic mechanisms have been identified that could mediate vertical transmission of epigenetic inheritance. However, relevance of these findings to human disease is not yet clear. An alternative model is one in which transgenerational inheritance of disease risk requires the presence of exposure-related diseases in the mother during pregnancy (termed induced epigenetic transmission model). A number of cross-sectional studies have investigated multigenerational effects in allergy and asthma. However, given the early-life origins of asthma and allergy, birth cohort studies are ideal to investigate the effect of genetic predisposition, epigenetics, and environmental exposures, avoiding pitfalls, such as recall bias and confounding by ongoing exposures, disease, and treatment. The well-characterized 3 generations of the Isle of Wight cohort include 2 consecutive birth cohorts, providing longitudinal data that can be studied for epigenetic transfer of information, such as the effect of grand parental smoking or exposure to other toxic compounds. Further large multigenerational birth cohorts are needed to establish the clinical relevance of this phenomenon and differentiate between vertical and induced transmission models, which might influence future preventive strategies.

Keywords: Cohort; DNA methylation; allergy; asthma; epigenetics; multigenerational.

Figure 1. Three generations of the Isle of Wight birth cohort

The birth cohort participants were recruited in 1989–90 and have been assessed at 1, 2, 4, 10, 18 and 27 years. Data and samples were collected from the parents of the cohort in 1989–90. The third generation (children of the original birth cohort) have been recruited since 2010 and to date assessed at 3, 12, 24, 36 and 60 months.

Figure 2. Vertical and induced epigenetic transmission models

Vertical epigenetic transmission model proposes direct transfer of epigenetic information from parents to child in successive generations (A). The alternative model, induced epigenetic transmission, proposes that maternal disease is an essential element in the chain of epigenetic transmission of information (B). DNA-M: DNA methylation