Genotype-expression interactions for BDNF across human brain regions.
Genotype-expression interactions for BDNF across human brain regions.
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BDNF基因型-表达相互作用在人类大脑区域。
DOI：
10.1186/s12864-021-07525-1
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发表时间：
2021-03-23
期刊：
影响因子：
4.4
通讯作者：
Stanfill AG
中科院分区：
文献类型：
--
作者：
Devlin P;Cao X;Stanfill AG
脑源性神经营养因子（BDNF）的遗传变异与各种精神疾病有关，包括抑郁症，强迫症，物质使用障碍和精神分裂症;这些遗传变异引发的基因表达改变可能有助于产生这些表型。但是这种基因的基因型-表达相互作用在与精神疾病相关的大脑区域中还没有得到很好的研究。在错误发现率（FDR）为10%（q < 0.1）时，小脑中共有61个SNP（n = 209）与BDNF表达相关，皮层中有55个SNP（n = 205），延髓核中有48个SNP（n = 202），尾状核中有47个SNP（n = 194），小脑半球中有58个SNP（n = 175）。我们在2个单倍型区块中确定了一组30个SNP，这些SNP与这5个区域中每个区域的表达改变相关。第一个单倍型块包括文献中与惊恐障碍（rs 16917204）、成瘾（rs 11030104）、双相情感障碍（rs 16917237/rs 2049045）和强迫症（rs6265）相关的变异。同样，第二个单倍型区块中的变异先前与尼古丁成瘾、重度抑郁症（rs 988748）和癫痫（rs6484320/rs7103411）等疾病相关。这项工作支持BDNF内的变体与这些关键脑区的表达变化相关，这些变化可能有助于强迫症，冲动和成瘾的常见行为表型。这些SNPs应该作为可能的治疗和诊断靶点进一步研究，以帮助管理这些和其他精神疾病。在线版本包含补充材料，可通过10.1186/s12864-021-07525-1获得。
Genetic variations in brain-derived neurotrophic factor (BDNF) are associated with various psychiatric disorders including depression, obsessive-compulsive disorder, substance use disorders, and schizophrenia; altered gene expression triggered by these genetic variants may serve to create these phenotypes. But genotype-expression interactions for this gene have not been well-studied across brain regions relevant for psychiatric disorders. At false discovery rate (FDR) of 10% (q < 0.1), a total of 61 SNPs were associated with BDNF expression in cerebellum (n = 209), 55 SNPs in cortex (n = 205), 48 SNPs in nucleus accumbens (n = 202), 47 SNPs in caudate (n = 194), and 58 SNPs in cerebellar hemisphere (n = 175). We identified a set of 30 SNPs in 2 haplotype blocks that were associated with alterations in expression for each of these 5 regions. The first haplotype block included variants associated in the literature with panic disorders (rs16917204), addiction (rs11030104), bipolar disorder (rs16917237/rs2049045), and obsessive-compulsive disorder (rs6265). Likewise, variants in the second haplotype block have been previously associated with disorders such as nicotine addiction, major depressive disorder (rs988748), and epilepsy (rs6484320/rs7103411). This work supports the association of variants within BDNF for expression changes in these key brain regions that may contribute to common behavioral phenotypes for disorders of compulsion, impulsivity, and addiction. These SNPs should be further investigated as possible therapeutic and diagnostic targets to aid in management of these and other psychiatric disorders. The online version contains supplementary material available at 10.1186/s12864-021-07525-1.
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影响因子：
6.4
作者：
Gamero-Villarroel, Carmen;Gordillo, Inmaculada;Gervasini, Guillermo
通讯作者：
Gervasini, Guillermo
影响因子：
6.1
作者：
Issa, George;Wilson, Christina;Pillai, Anilkumar
通讯作者：
Pillai, Anilkumar
影响因子：
4.2
作者：
Kight, Katherine E.;McCarthy, Margaret M.
通讯作者：
McCarthy, Margaret M.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
DOI：
10.1093/gerona/glx152
发表时间：
2018-02-01
影响因子：
5.1
作者：
Arvanitakis, Zoe;Capuano, Ana W.;Barnes, Lisa L.
通讯作者：
Barnes, Lisa L.