کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
341668 548541 2007 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Extensive linkage disequilibrium mapping at HTR2A and DRD3 for schizophrenia susceptibility genes in the Galician population
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
Extensive linkage disequilibrium mapping at HTR2A and DRD3 for schizophrenia susceptibility genes in the Galician population
چکیده انگلیسی

The serotonin and dopamine neurotransmitter systems are candidate pathways in the development of schizophrenia because of the assumed causal relationship with the observed symptoms as well as effective targeting of the corresponding receptors by antipsychotic drugs. However, genetic association studies have systematically focused on a limited set of genes and single nucleotide polymorphisms (SNPs), including T102C at HTR2A and Ser9Gly at DRD3. Meta-analyses of the associations between these two markers and schizophrenia revealed a true increase in risk, the magnitude of the effect being very low. In the present study we analyzed 260 schizophrenic patients and 354 control subjects from a homogeneous population, the Galician population, using an extensive linkage disequilibrium (LD) mapping approach, genotyping a total of 47 SNPs to test for the existence of additional variants that confer higher risk. We detected nominal significant association with schizophrenia for several haplotype tag SNPs (htSNPs) at HTR2A, although the significance was lost after multiple test corrections. In addition, haplotype analyses involving a sliding window approach, with window size 2 to 4 SNPs, revealed significant differences in frequencies of the DRD3 haplotypes at the 3′ half of the gene region. This difference, which remains clearly significant after multiple test corrections (p = 0.002, 0.0001, and 0.0025, for window sizes 2, 3, and 4, respectively), was mainly due to over-representation of several rare haplotypes in patients, at the expense of a single common haplotype; this represents interesting evidence of rare haplotypes for susceptibility detected using common htSNPs due to their strong effect.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Schizophrenia Research - Volume 90, Issues 1–3, February 2007, Pages 123–129
نویسندگان
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