title: Genetic and phenotypic approach to understanding reading ability and associated health and lifestyle outcomes in the national child development study
title: A genetic and phenotypic approach to understanding reading ability and associated health and lifestyle outcomes in the national child development study
titleType: AlternativeTitle
Creators: name: Bridges, Elinor C.
Publisher: name: The University of Edinburgh
Year: 2024
Subjects: reading ability
reading ability and associated health and lifestyle outcomes
national child development study
polygenic trait
socioeconomic status (SES)
reading and back pain
reading and rheumatism

description: Reading ability is a polygenic trait, which is also influenced by environment. Despite the global social and economic cost of poor reading skills, molecular genetic research regarding reading ability as a quantitative trait is still in its infancy. Modern molecular methods have the potential to reveal much about such complex traits, including their genetic basis and how they relate to other traits. Chapter 1 explores the literature around reading ability, including how reading skills are defined, and the predictors and outcomes associated with them. Chapter 2 reviews the current state of knowledge on the genetics of reading ability, including studies from family, twin, and molecular genetic designs. This thesis has utilised the National Child Development Study (NCDS) to investigate longitudinal reading, the genetics of reading, and associations with other traits in detail. Chapter 3 reviews the cohort in more detail, including the data available and a review of existing reading research in the dataset. Chapter 4 outlines the genetics methods that are used to carry out the empirical research in the remainder of the thesis, including genotype imputation, genome-wide association studies, and linkage disequilibrium score based genetic correlations. The NCDS is a UK based birth cohort study, which has been running since 1958. A subsample of NCDS participants have provided genetic data, however this genomic dataset has been poorly documented. In Chapter 5, I present an updated version of the NCDS genomic dataset, which has been imputed to the Haplotype Reference Consortium v1.1 reference panel, for use in future research (n = 6431). This contribution will allow other researchers to carry out analysis using modern molecular methods on a dataset imputed to a reference panel which has been shown to be more effective than the previous reference panel the NCDS was imputed to, the 1000 Genomes reference panel. The NCDS contains a series of different reading measures, including objective tests, teacher ratings, and self-report measures, from childhood though to midlife. In Chapter 5, these measures have been analysed to develop a series of reliable and valid age-specific indices which measure reading ability quantitatively, with potential to be used in future reading research. Chapter 6 uses reading composites as the phenotype outcome for a series of genetic analyses, which replicate several previous findings, showing that the reading composites generated in the NCDS, while not gold standard reading assessments, are still appropriate measures of reading ability. Genome-wide association analysis was conducted on reading ability composites derived at different ages through childhood to young adulthood. Downstream analysis showed the reading measures at different ages to be strongly genetically correlated with each other, with reading and language variables from other samples, and moderately genetically correlated with a series of additional traits related to social, educational, occupational and health outcomes, replicating several previous findings. Positive genetic correlations were found between reading and cognitive performance, educational attainment, and employment status, whereas negative genetic correlations were found between reading and occupational conditions, wellbeing measures, and health outcomes. This study replicated an earlier intriguing finding of a genetic correlation between reading and pain, which was then explored further by interrogating genetic correlations between reading and additional pain related variables, such as painkiller use. Given the richness of the NCDS longitudinal data, in Chapter 7 I further explored the association between reading ability and pain in an effort to disentangle potential causal relationships between the two. Logistic and linear regression analyses were used to analyse the association between childhood reading ability and experiencing pain in childhood and adulthood. Several pain types were tested, including abdominal pain and headache in childhood, and back pain, eye pain, headache, migraine, and rheumatism in adulthood. Numerous significant associations were discovered at multiple age points, with all significant associations indicating that better readers are less likely to experience pain. Further analysis indicated that socioeconomic status (SES) may act as a mediator for the relationship between reading and some pain types. Evidence of full mediation was found for the relationship between reading and back pain, while evidence regarding a mediation effect between reading and rheumatism was unclear. SES, measured by occupation, did not mediate the relationship between reading and eye pain, and the results indicated that reading ability and SES acted together to influence headache. I conducted post-hoc analysis in an attempt to further untangle the relationship between reading and back pain, including physical demands of the participant’s job as a covariate. The mediation effect remained, indicating that mediation was due to other elements of SES. Chapter 8 explores the further implications of this research. This thesis shows that non-validated reading measures can be combined in order to generate a reliable and valid quantitative reading composite that is suitable for further research in reading, including genetic research. This is significant, as the NCDS is an exceptionally rich longitudinal dataset, which has the potential to be used to study gene by environment interactions in future reading research using molecular methods, an area with potential which is still in its infancy. This work has added to a small amount of existing molecular evidence which suggests that reading is genetically stable over time, with high genetic correlations found between reading at ages seven, eleven, sixteen, and an overall reading composite including measures from childhood through to age 33. Additionally, this thesis replicated previously identified genetic correlations between reading ability and health, including pain. Phenotypic analysis has indicated that, in some cases, the relationship is not due to SES, and therefore it is possible that pain and reading ability share a biological mechanism; future research using multivariate genetic methods (expanding to other neurodevelopmental traits) are needed to identify these common biological causes. Finally, this thesis has shown that the richness of the NCDS dataset, combined with genetic information, proves it valuable for behaviour genetic reading research. With much still to discover about the behaviour genetics of reading ability and its transactions with the environment, this thesis will hopefully act as a starting point for further work in this area, which should include a thorough investigation of gene by environment correlation and interaction in reading ability.