Abstract
Myopia (near sightedness) is the most common vision disorder resulting in visual impairment worldwide. We tested the hypothesis that intergenerational, non-genetic heritable effects influence refractive development, using grandparental prenatal smoking as a candidate exposure. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we found that the prevalence of myopia at age 7 was lower if the paternal grandmother had smoked in pregnancy, an association primarily found among grandsons compared to granddaughters. There was a weaker, non-sex-specific, reduction in the prevalence of myopia at age 7 if the maternal grandmother had smoked in pregnancy. For children who became myopic later (between 7 and 15 years of age) there were no associations with either grandmother smoking. Differences between early and late-onset myopia were confirmed with DNA methylation patterns: there were very distinct and strong associations with methylation for early-onset but not later-onset myopia.
Highlights
Little can be said about direction of effect, i.e. whether DNA methylation differences played a role in myopia or myopia a role in DNA methylation differences
We conclude that: (i) Intergenerational associations observed were confined to early onset myopia at age 7
No associations were observed with myopia developing between 7 and 15 years, supporting the view that these two groups have different etiologies
Summary
The data used in these analyses were collected as part of the Avon Longitudinal Study of Parents and Children (ALSPAC), which was designed to assess the ways in which the environment interacts with the genotype to influence health and development[46,47,48]. The initial ALSPAC sample consisted of 14,541 pregnancies; of these initial pregnancies, there was a total of 14,676 fetuses, resulting in 14,062 live births and 13,988 children who were alive at 1 year of age. Information on the cohort parents and their offspring was collected using a variety of methodologies including self-completion questionnaires sent to study mothers, fathers, teachers and the study child, direct examination under standardized conditions, and linkage to educational data from the school system. Please note that the study website contains details of all the data that is available through a fully searchable data dictionary and variable search tool (http://www.bristol.ac.uk/alspac/researchers/our-data/)
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