Association of DCDC2 Polymorphisms with Normal Variations in Reading Abilities in a Chinese Population.

The doublecortin domain-containing 2 (DCDC2) gene, which is located on chromosome 6p22.1, has been widely suggested to be a candidate gene for dyslexia, but its role in typical reading development over time remains to be clarified. In the present study, we explored the role of DCDC2 in contributing to the individual differences in reading development from ages 6 to 11 years by analysing data from 284 unrelated children who were participating in the Chinese Longitudinal Study of Reading Development (CLSRD). The associations of eight single nucleotide polymorphisms (SNPs) in DCDC2 with the latent intercept and slope of children's reading scores were examined in the first step. There was significant support for an association of rs807724 with the intercept for the reading comprehension measure of reading fluency, and the minor "G" allele was associated with poor reading performance. Next, we further tested the rs807724 SNP in association with the reading ability at each tested time and revealed that, in addition to significant associations with the two main reading measures (reading fluency and Chinese character reading) over multiple testing occasions, this SNP also showed associations with reading-related cognitive skills, including morphological production, orthographic judgment and phonological processing skills (rapid number naming, phoneme deletion, and tone detection). This study provides support for DCDC2 as a risk gene for reading disability and suggests that this gene is also operative for typical reading development in the Han population.

Association of the DYX1C1 dyslexia susceptibility gene with orthography in the Chinese population.

Several independent studies have supported the association of DYX1C1 with dyslexia, but its role in general reading development remains unclear. Here, we investigated the contribution of this gene to reading, with a focus on orthographic skills, in a sample of 284 unrelated Chinese children aged 5 to 11 years who were participating in the Chinese Longitudinal Study of Reading Development. We tested this association using a quantitative approach for Chinese character reading, Chinese character dictation, orthographic judgment, and visual skills. Significant or marginally significant associations were observed at the marker rs11629841 with children's orthographic judgments at ages 7 and 8 years (all P values<0.020). Significant associations with Chinese character dictation (all P values<0.013) were also observed for this single-nucleotide polymorphism (SNP) at ages 9, 10, and 11 years. Further analyses revealed that the association with orthographic skills was specific to the processing of specific components of characters (P values<0.046). No association was found at either SNP of rs3743205 or rs57809907. Our findings suggest that DYX1C1 influences reading development in the general Chinese population and supports a universal effect of this gene.

SSRI response in depression may be influenced by SNPs in HTR1B and HTR1A.

OBJECTIVES: Desensitization of serotonin 1A (HTR1A) and 1B (HTR1B) autoreceptors has been proposed to be involved in the delayed onset of response to selective serotonin reuptake inhibitors (SSRIs). Variations in gene expression in these genes may thus affect SSRI response. METHODS: Here, we test this hypothesis in two samples from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D), and show evidence for involvement of several genetic variants alone and in interaction. Initially, three functional single nucleotide polymorphisms (SNPs) in the HTR1B gene and in the HTR1A gene were analyzed in 153 depressed patients treated with citalopram. The 16-item Quick Inventory of Depressive Symptomatology Clinician scores were evaluated over time with respect to genetic variation. RESULTS: Individuals homozygous for the -1019 G allele (rs6295) in HTR1A showed the higher baseline 16-item Quick Inventory of Depressive Symptomatology Clinician scores (P=0.033), and by 12 weeks had a significantly lower response rate (P=0.005). HTR1B haplotypes were estimated according to the previously reported in-vitro expression levels. Individuals who were homozygous for the high-expression haplotype showed significantly slower response to citalopram (P=0.034). We then analyzed more SNPs in the extended overall STAR*D sample. Although we could not directly test the same functional SNPs, we found that homozygotes for the G allele at rs1364043 in HTR1A (P=0.045) and the C allele of rs6298 in HTR1B showed better response to citalopram over time (P=0.022). Test for interaction between rs6298 in HTR1B and rs1364043 in HTR1A was significant (overall P=0.032). CONCLUSION: Our data suggest that an enhanced capacity of HTR1B or HTR1A transcriptional activity may impair desensitization of the autoreceptors during SSRI treatment.

Gene-based SNP genetic association study of the corticotropin-releasing hormone receptor-2 (CRHR2) in major depression.

An increasing amount of data suggests that affective disorders are related to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, the stress-response system. Corticotropin-releasing hormone receptor-2 (CRHR2)-deficient mice display a stress-sensitive and anxiety-like phenotype suggesting that the CRHR2 is a plausible functional candidate gene influencing the reactivity of the HPA axis and therefore the liability to develop affective disorders. In this study, a gene-based single nucleotide polymorphism (SNP) map of the corticotropin-releasing hormone receptor 2 (CRHR2) was constructed containing one synonymous cSNP in exon 10, two intronic SNPs, and two SNPs in the 5' upstream regulatory region. No significant difference in allele or genotype frequency was found for four out of the five SNPs between Belgian unipolar (UP) patients and age-, gender-, and ethnicity-matched controls. The cSNP did show allelic and genotypic association with borderline significance (P=0.04). However, a replication study of this cSNP in a bipolar sample of Belgian origin and a Swedish UP sample did not show significant differences in allele and genotype frequencies.