Multi-generational cohorts in asthma and allergy

Abstract

Recent observations that disease risk can be transmitted across generations, without the need for a direct exposure of the child to the index environmental insult, has sparked interest in transgenerational inheritance. Epigenetic describes processes that modify gene expression without a change in the nucleotide sequence. Epigenetic processes can be induced in response to environmental exposures and can influence disease risk, and may 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 where 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 early life origins of asthma and allergy, birth cohort studies are ideal to investigate the impact of genetic predisposition, epigenetics, and environmental exposures avoiding pitfalls such as recall bias and confounding by ongoing exposures, disease and treatment. The well characterized, three generations of the Isle of Wight cohort includes two consecutive birth cohorts, providing longitudinal data that can be studied for epigenetic transfer of information, e.g., 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 may influence future preventive strategies.

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Identifiers

ORCID for John W. Holloway: orcid.org/0000-0001-9998-0464

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