Interaction between risk SNPs of Developmental Dyslexia and Parental Education on Reading Ability: Evidence for Differential-Susceptibility Theory

While genetic and environmental factors have been shown as predictors of children’s reading ability, the interaction effects of identified genetic risk susceptibility and specified environmental for reading ability have rarely been investigated. The current study assessed potential gene-environmental (G×E) interactions on reading ability in 1477 school-aged children. The gene-environment interactions on character recognition were investigated by an exploration analysis between the risk single-nucleotide polymorphisms (SNPs) which were discovered by previous genome-wide association studies of developmental dyslexia (DD), and parental education (PE). The re-parameterized regression analysis suggested that this G×E interaction conformed to the strong differential-susceptibility model. Results showed that rs281238 exhibits a significant interaction with PE on character recognition. Children with “T” genotype profited from high PE, whereas they performed worse in low PE environment, but “CC” genotype children were not malleable in different PE environments. Research Highlights ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was funded by National Natural Science Foundation of China （61807023）, Funds for Humanities and Social Sciences Research of the Ministry of Education (CN) (17XJC190010), Natural Science Foundation of Shaanxi Province (CN) (2018JQ8015), and Fundamental Research Funds for the Central Universities (CN) (GK201702011) to Jingjing Zhao. This study was also funded by Fund for Humanities and Social Sciences Research of the Ministry of Education (19YJC190023), and the China Postdoctoral Science Foundation funding project (2019M663924XB), Natural Science Foundation of Shaanxi Province (CN) (2021JQ-309), and Planning Subject for the 14th Five Year Plan of Shaanxi Education Sciences (SGH21Y0040) to Zhengjun Wang. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval was obtained from Shaanxi Normal University and written informed consent was obtained for all the participants' parents. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The beta values of the SNPs in this paper can be found in previous studies. The statistical methods and statistical data available from the corresponding author upon reasonable request. The raw data are not publicly available due to legal or ethical restrictions.