Genome-wide association analysis links multiple psychiatric liability genes to oscillatory brain activity.
Genome-wide association analysis links multiple psychiatric liability genes to oscillatory brain activity.
复制标题
DOI：
10.1002/hbm.24238
复制
发表时间：
2018-11
影响因子：
4.8
通讯作者：
Boomsma DI
中科院分区：
文献类型：
--
作者：
Smit DJA;Wright MJ;Meyers JL;Martin NG;Ho YYW;Malone SM;Zhang J;Burwell SJ;Chorlian DB;de Geus EJC;Denys D;Hansell NK;Hottenga JJ;McGue M;van Beijsterveldt CEM;Jahanshad N;Thompson PM;Whelan CD;Medland SE;Porjesz B;Lacono WG;Boomsma DI
振荡活动对于大脑的信息处理至关重要，并且作为精神病理学的生物标志物有着悠久的历史。振荡活动的变化具有高度遗传性，但目前对特定遗传影响的理解仍然有限。我们对 8,425 名受试者进行了迄今为止最大规模的全基因组关联研究，研究了闭眼静息脑电图 (EEG) 期间一系列频率（δ 1–3.75 Hz、θ 4–7.75 Hz、α 8–12.75 Hz 和 beta 13–30 Hz）的振荡功率。此外，我们还进行了基于 KGG 位置基因的分析和大脑表达分析。 GABRA2（一种已知的酒精使用障碍和癫痫遗传标记）显着影响 β 功率，与 GABAA 中间神经元活动和 β 振荡之间已知的关系一致。基于 GTEx 数据库的组织特异性 SNP 基因表达水平估算表明，海马 GABRA2 表达可能介导这种效应。 3p21.1 处的 24 个基因对于 alpha 功率具有显着性 (FDR q < .05)。该区域的 SNP 与海马组织中 GLYCTK 的表达以及额叶皮质中 GNL3 和 ITIH4 的表达有关，这些基因先前与精神分裂症和双相情感障碍有关。总之，我们发现了几种与大脑振荡活动相关的新基因变异。此外，我们复制并加深了对先前已知的与精神病理学（即精神分裂症和酒精使用障碍）相关基因的理解。重要的是，这些精神病理学责任基因影响大脑功能，将基因的表达与特定的皮质/皮质下大脑区域联系起来。
Oscillatory activity is crucial for information processing in the brain, and has a long history as a biomarker for psychopathology. Variation in oscillatory activity is highly heritable, but current understanding of specific genetic influences remains limited. We performed the largest genome‐wide association study to date of oscillatory power during eyes‐closed resting electroencephalogram (EEG) across a range of frequencies (delta 1–3.75 Hz, theta 4–7.75 Hz, alpha 8–12.75 Hz, and beta 13–30 Hz) in 8,425 subjects. Additionally, we performed KGG positional gene‐based analysis and brain‐expression analyses. GABRA2—a known genetic marker for alcohol use disorder and epilepsy—significantly affected beta power, consistent with the known relation between GABAA interneuron activity and beta oscillations. Tissue‐specific SNP‐based imputation of gene‐expression levels based on the GTEx database revealed that hippocampal GABRA2 expression may mediate this effect. Twenty‐four genes at 3p21.1 were significant for alpha power (FDR q < .05). SNPs in this region were linked to expression of GLYCTK in hippocampal tissue, and GNL3 and ITIH4 in the frontal cortex–genes that were previously implicated in schizophrenia and bipolar disorder. In sum, we identified several novel genetic variants associated with oscillatory brain activity; furthermore, we replicated and advanced understanding of previously known genes associated with psychopathology (i.e., schizophrenia and alcohol use disorders). Importantly, these psychopathological liability genes affect brain functioning, linking the genes' expression to specific cortical/subcortical brain regions.
登录
查看更多内容
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
9.8
作者：
Edenberg, HJ;Dick, DM;Begleiter, H
通讯作者：
Begleiter, H
影响因子：
3.2
作者：
Sung, Yun J.;de las Fuentes, Lisa;Rao, Dabeeru C.
通讯作者：
Rao, Dabeeru C.
影响因子：
30.8
作者：
Bulik-Sullivan B;Finucane HK;Anttila V;Gusev A;Day FR;Loh PR;ReproGen Consortium;Psychiatric Genomics Consortium;Genetic Consortium for Anorexia Nervosa of the Wellcome Trust Case Control Consortium 3;Duncan L;Perry JR;Patterson N;Robinson EB;Daly MJ;Price AL;Neale BM
通讯作者：
Neale BM
影响因子：
10.6
作者：
Arion, Dominique;Unger, Travis;Mirnics, Karoly
通讯作者：
Mirnics, Karoly