The genetic architecture of the human hypothalamus and its involvement in neuropsychiatric behaviours and disorders.
The genetic architecture of the human hypothalamus and its involvement in neuropsychiatric behaviours and disorders.
复制标题
人类下丘脑的遗传结构及其与神经精神行为和疾病的关系。
DOI：
10.1038/s41562-023-01792-6
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发表时间：
2024
影响因子：
29.9
通讯作者：
Chen SD
中科院分区：
文献类型：
--
作者：
Chen SD
尽管下丘脑在调节重要代谢和神经功能方面发挥着至关重要的作用，但其遗传结构仍然未知。在这里，我们使用 32,956 名个体的下丘脑成像数据进行了多变量全基因组关联研究 (GWAS)，以揭示下丘脑的遗传基础及其与神经精神特征的关系。有 23 个与整个下丘脑及其亚基相关的显着位点，其中涉及细胞内运输系统和类固醇相关化合物代谢过程的基因功能富集。下丘脑表现出与边缘系统结构和神经精神特征（包括时间型、危险行为、认知、饱腹感和交感-副交感神经活动）显着的遗传关联。主要 GWAS 中最强的信号，即 ADAMTS8 位点，在三个独立数据集中 (N= 1,685–4,321) 进行了复制，并在荟萃分析后得到了加强。全外显子组关联分析为 ADAMTS8 的关联添加了证据，孟德尔随机化显示下丘脑体积越大，ADAMTS8 表达越低。目前的研究增进了我们对下丘脑复杂结构与功能关系的理解，并提供了对下丘脑形成的分子机制的见解。
Despite its crucial role in the regulation of vital metabolic and neurological functions, the genetic architecture of the hypothalamus remains unknown. Here we conducted multivariate genome-wide association studies (GWAS) using hypothalamic imaging data from 32,956 individuals to uncover the genetic underpinnings of the hypothalamus and its involvement in neuropsychiatric traits. There were 23 significant loci associated with the whole hypothalamus and its subunits, with functional enrichment for genes involved in intracellular trafficking systems and metabolic processes of steroid-related compounds. The hypothalamus exhibited substantial genetic associations with limbic system structures and neuropsychiatric traits including chronotype, risky behaviour, cognition, satiety and sympathetic–parasympathetic activity. The strongest signal in the primary GWAS, theADAMTS8locus, was replicated in three independent datasets (N= 1,685–4,321) and was strengthened after meta-analysis. Exome-wide association analyses added evidence to the association forADAMTS8, and Mendelian randomization showed lowerADAMTS8expression with larger hypothalamic volumes. The current study advances our understanding of complex structure–function relationships of the hypothalamus and provides insights into the molecular mechanisms that underlie hypothalamic formation.
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影响因子：
11
作者：
International Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and OCD Collaborative Genetics Association Studies (OCGAS)
通讯作者：
International Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and OCD Collaborative Genetics Association Studies (OCGAS)
影响因子：
29.9
作者：
Sha Z;Schijven D;Carrion-Castillo A;Joliot M;Mazoyer B;Fisher SE;Crivello F;Francks C
通讯作者：
Francks C
影响因子：
30.8
作者：
Pardiñas AF;Holmans P;Pocklington AJ;Escott-Price V;Ripke S;Carrera N;Legge SE;Bishop S;Cameron D;Hamshere ML;Han J;Hubbard L;Lynham A;Mantripragada K;Rees E;MacCabe JH;McCarroll SA;Baune BT;Breen G;Byrne EM;Dannlowski U;Eley TC;Hayward C;Martin NG;McIntosh AM;Plomin R;Porteous DJ;Wray NR;Caballero A;Geschwind DH;Huckins LM;Ruderfer DM;Santiago E;Sklar P;Stahl EA;Won H;Agerbo E;Als TD;Andreassen OA;Bækvad-Hansen M;Mortensen PB;Pedersen CB;Børglum AD;Bybjerg-Grauholm J;Djurovic S;Durmishi N;Pedersen MG;Golimbet V;Grove J;Hougaard DM;Mattheisen M;Molden E;Mors O;Nordentoft M;Pejovic-Milovancevic M;Sigurdsson E;Silagadze T;Hansen CS;Stefansson K;Stefansson H;Steinberg S;Tosato S;Werge T;GERAD1 Consortium;CRESTAR Consortium;Collier DA;Rujescu D;Kirov G;Owen MJ;O'Donovan MC;Walters JTR
通讯作者：
Walters JTR
学习是一个历史问题并且与外侧下丘脑相关
影响因子：
25
作者：
S. Floresco
通讯作者：
S. Floresco
影响因子：
29
作者：
Ishii M;Iadecola C
通讯作者：
Iadecola C