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Psychiatric genetics (1)
Burmeister, Margit (2)
Villafuerte, Sandra M. (2)
Li, Hong (1)
Li, Jun (1)
Liang, Weilan (1)
McBride-Chang, Catherine (1)
McMahon, Francis J. (1)
Penney, Trevor Bruce (1)
Shi, Bingjie (1)
Shu, Hua (1)
Tardif, Twila (1)
Vallabhaneni, Kamala (1)
Young, Elizabeth A. (1)
Zhang, Yuping (1)
Zhang, Zhixiang (1)
Śliwerska, Elżbieta (1)
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author:("villaverde, Sandra M.")
SSRI response in depression may be influenced by SNPs in HTR1B and HTR1A
McMahon, Francis J.
Young, Elizabeth A.
Desensitization of serotonin 1A (HTR1A) and 1B (HTR1B) autoreceptors has been proposed to be involved in the delayed onset of response to SSRIs. Variations in gene expression in these genes may thus affect SSRI response. 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 SNPs in the HTR1B gene and in the HTR1A gene were analyzed in 153 depressed patients treated with citalopram. QIDS-C scores were evaluated over time with respect to genetic variation. Subjects homozygous for the - 1019 G allele (rs6295) in HTR1A showed higher baseline QIDS scores (p = 0.033), and by 12 weeks had a significantly lower response rate (p = 0.005). HTR1B haplotypes were estimated according to 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)
Our data suggest that an enhanced capacity of HTR1B or HTR1A transcriptional activity may impair desensitization of the autoreceptors during SSRI treatment.
SSRI; depression; haplotype; HTR1B; HTR1A; association
Association of the DYX1C1 Dyslexia Susceptibility Gene with Orthography in the Chinese Population
Penney, Trevor Bruce
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.
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