Proficient reading is critical for success in school as well as lifetime earning potential. Children with low reading ability are more likely to live in poverty and have higher rates of unemployment as adults1. A great deal of research has been devoted to investigating the predictors of reading outcomes, including measures of individual word reading and reading comprehension, but the general consensus among reading researchers is that phonological processing skill, particularly phonological awareness, is a significant determinant of reading outcome2,3. Phonological processing refers to the use of phonological information in decoding written language4. Children with advanced phonological skills tend to have successful reading outcomes, whereas lower phonological skill is associated with reading difficultie5,6.
In addition to phonological skills, reading is also influenced by genetic factors. In studies of twins, the heritability of reading is high, ranging from .46 to .72 7,8. However, heritability estimates are not uniformly high in molecular genetic studies of unrelated individuals assessed with single nucleotide polymorphisms (SNPs). While the differences in heritability estimates between family studies and SNP studies in psychiatric disorders is well known – frequently characterized as “missing heritability” – it is also likely that the relationship between genes and reading is indirect. Few studies rigorously address the connection between genes and reading outcomes. The prominent role of phonological skill in reading performance suggests that it may function as a mediator between specific genes and reading proficiency.
Approximately 18 genes have been associated with reading performance, but association with only 8 genes has been replicated three or more times: CMIP, ATP2C2, FOXP2, ROBO1, DYXC1, KIAA0319, DCDC2, and CNTNAP2 9. Among them, only KIAA0319 and DCDC2 are located in the most replicated reading locus (DYX2; chromosome 6p22), and within both genes the peaks of association lie within regulatory features. We previously showed that we could identify children with a specific phonological deficit with variants of READ1, a regulatory element encoded within a known RD risk gene called DCDC2 10,11.
Home environment is another factor related to reading and it can influence the relationship between genetics and reading. The variance due to genetic influence varies because home environment moderates genetic influences on reading outcomes12. Home environment may function as a condition on the mediating effect of phonological skill in the gene-reading linkage. In the present study, we aimed to examine the mediating role of phonological awareness between genes and reading. We were also interested in the moderating role of home environment to influence this mediation effect. By simultaneously considering the roles of phonological awareness and home environment, a moderated mediation model was tested to provide guidance in understanding how genetics affects reading performance.
1.1. The Connection between Phonological Processing and Reading Outcomes
It is well established that developmental and individual differences in phonological processing are causally related to reading ability in both longitudinal and experimental research2,13. Furthermore, deficit in phonological processing is a contributor to reading disability14,15.
Phonological awareness, a major component of phonological processing, refers to the sensitivity to and ability to manipulate sounds or sound structures of words. It is a powerful concurrent and longitudinal predictor of reading development3,4,16. According to the phonological deficit hypothesis, phonological awareness is a critical factor explaining difficulties in reading17. Interventions on phonological awareness training prove to be effective in improving reading performance of children with reading disability5. Thus, the connections between phonological awareness and rapid automatized naming and reading outcomes are well established and evidenced.
1.2. The Connection between Genetics and Reading Outcomes
The research showed significant and substantial genetic influences on reading performance18. For those who have difficulties in reading, research has shown that reading problems tend to run in families19. Twin studies research has shown large genetic influences on both word reading and reading comprehension from samples in Colorado, Ohio, Florida, England, Australia, and Scandinavia7,20,21,22,23. Although behavioral genetics studies can tell us whether reading is affected by genetic influences, they do not tell us which risk gene(s) can influence reading. This issue points to the high need of molecular genetics research.
Patterns of heritability toward genetic contribution and molecular genetics have identified risk genes that may cause reading difficulties10, 24, 25, 26, 27. Among the identified risk genes that are associated with reading difficulties, DCDC2, located on chromosome 6p22, is the most replicated risk gene10,11. Research has shown that READ1 (regulatory element associated with dyslexia 1) is a regulatory element encoded in intron 2 of DCDC2 and is a highly polymorphic complex tandem repeat with at least 40 alleles10,11,28,29. Among these alleles, RU2-Short that includes 6 or fewer copies of repeat unit 2 (alleles 4, 10, and 16 etc.) is considered a highly risk genetic variant of reading difficulties30. Clinical studies showed READ1 allele-specific association with severe reading and language impairment29. Nevertheless, the identified genes account for only a small portion of variance in reading difficulties31. The READ1 in the DYX2 locus should be further studied for its effects on reading performance.
1.3. The Connection between Genetics and Phonological Awareness
Previous studies have consistently found genetic influence on phonological awareness8,32,33. Furthermore, studies have shown that genes are responsible for the interrelations among phonological awareness and reading-related outcomes. For example, genetic influences were found to explain the comorbidity among phonological and orthographic skills8 or covariance between phonological awareness, rapid naming, and reading outcomes33.
1.4. The Genetic x Environment Influence on Reading
Home environment is crucial in literacy development. Parental education and socioeconomic status (SES) are important indicators of home environment34,35,36,37,38. Education is considered one of the most stable variables as it is usually established early in life and does not change over time. Parental education is highly correlated with children’s reading achievement39,40. SES is typically the most direct measure of family wealth and meta-analyses have demonstrated that SES is highly correlated with student achievement40,41.
Two models have been proposed to understand the relationship between genetic and environmental influences (G x E) on reading. One is the bioecological model which indicated that genetic influences should be greater in advantaged environment because genetic potential would be more fully realized in the supportive environments than in the poor environments42. The other is the diathesis-stress model which suggested that heritability should be greater in poor environments because deleterious genes may not be observed in more supportive environments. Both models are reasonable accounts of G x E interactions on reading. For example, individuals who carry the deleterious genes to put them as being reading disabled may experience the disadvantaged environment and such environmental triggers can activate deleterious genetic influences. Conversely, individuals who have the good genes may experience the supportive environments which may realize this genetic potential.
G x E interactions have been examined in reading abilities and disabilities1,12,20, 43 but the findings are mixed. For example, Kremen et al. (2005) 43 found a shared environment x parental education interaction but not genetic x parental education interaction in a middle-aged men sample. This finding was confirmed by Taylor and Schatschneider’s (2010) study20. In Taylor and Schatschneider (2010), greater shared environmental influence than genetic influences were observed for first grade reading for the low-income group but not for the middle and high income groups. In contrast, Friend, DeFries, and Olson (2008)1 examined 545 identical and fraternal twins with at least one member of the pair who had the reading disability. They reported a G x E interaction and found that genetic influence was higher and environmental influence was lower among children whose parents had a high level of education. The heritability of low reading ability was significantly higher among children whose parents had higher levels of education, indicating that parental education moderated genetic influences on reading disability. Friend et al. (2009)12 further explored identical and fraternal twins with typically developing reading abilities from US and UK and reported that the heritability of high reading ability increased significantly with lower levels of parental education in both samples. Children whose parents had lower levels of education tend to have stronger genetic influence on their high reading ability. However, in a similarly aged sample, no moderating effects of parental education on genetic influences were found44. In addition, brain-behavior relationships critical for reading development are more pronounced in low SES environments45.
Overall, the findings from G x E interactions on reading ability are mixed. Much of the research on these topics has focused on behavioral genetics rather than molecular genetics and the G x E interaction research is mainly limited to twin studies. Further research is necessary to understand how genes interact with environment to affect reading ability. Ideally, a study testing this moderating effect should include molecular genetics with the identified genes that influence reading.