Multigenerational cohorts in patients with asthma and allergy.
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.
David Hide Asthma and Allergy Research Centre, Isle of Wight, United Kingdom; Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom. Electronic address: sha@soton.ac.uk.
S Hasan
SH
Arshad
Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis, Memphis, Tenn.
Wilfried
W
Karmaus
Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis, Memphis, Tenn.
Hongmei
H
Zhang
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; Human Development and Health, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, United Kingdom.
John W
JW
Holloway
D001249:Asthma / Q000235:genetics*; D015331:Cohort Studies; D019175:DNA Methylation; D004781:Environmental Exposure / Q000009:adverse effects; D044127:Epigenesis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D040941:Heredity / Q000235:genetics* / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics*; D018811:Maternal Exposure / Q000009:adverse effects; D012306:Risk
Cohort; DNA methylation; allergy; asthma; epigenetics; multigenerational