Chromosomal inversion polymorphisms shape human brain morphology.
Chromosomal inversion polymorphisms shape human brain morphology.
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染色体倒位多态性塑造人脑形态。
DOI：
10.1016/j.celrep.2023.112896
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发表时间：
2023-08-29
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
染色体倒位对人脑形态的影响仍有待研究。我们研究了从33，018名欧洲血统成年人的基因型中分类的35种常见倒位。2p22.3、16p11.2和17q21.31的倒位达到全基因组意义，其次是8p23.1和6p21.33，与皮质和皮质下形态学相关。17q21.31、8p23.1和16p11.2区域包含LRRC37、OR7E和NPIP重复基因家族。我们发现17q21.31 MAPT倒位区域，以窝藏神经风险而闻名，是塑造和图案化皮层的常见变体中最突出的位点。总的来说，我们观察到反向方向减少大脑的大小，除了2p22.3反转与皮质下体积增加和8p23.1反转与运动皮质增加。这些重要的倒位位于神经精神基因座的基因组热点。我们的研究结果可推广到3，472名儿童，并证明倒位是理解人类大脑表型的必要遗传变异。Wang等人证明倒位多态性位于神经精神基因座的基因组热点内，并与脑形态学相关。这项研究强调，倒位多态性，沿着与其他遗传变异，发挥了重要作用的贡献者的表型多样性观察大脑发育和疾病。
The impact of chromosomal inversions on human brain morphology remains underexplored. We studied 35 common inversions classified from genotypes of 33,018 adults with European ancestry. The inversions at 2p22.3, 16p11.2, and 17q21.31 reach genome-wide significance, followed by 8p23.1 and 6p21.33, in their association with cortical and subcortical morphology. The 17q21.31, 8p23.1, and 16p11.2 regions comprise the LRRC37, OR7E, and NPIP duplicated gene families. We find the 17q21.31 MAPT inversion region, known for harboring neurological risk, to be the most salient locus among common variants for shaping and patterning the cortex. Overall, we observe the inverted orientations decreasing brain size, with the exception that the 2p22.3 inversion is associated with increased subcortical volume and the 8p23.1 inversion is associated with increased motor cortex. These significant inversions are in the genomic hotspots of neuropsychiatric loci. Our findings are generalizable to 3,472 children and demonstrate inversions as essential genetic variation to understand human brain phenotypes. Wang et al. demonstrate that inversion polymorphisms are located within the genomic hotspots of neuropsychiatric loci and are linked to brain morphology. This study emphasizes that inversion polymorphisms, along with other genetic variants, play a significant role as contributors to the phenotypic diversity observed in brain development and disorders.
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影响因子：
64.8
作者：
Elliott LT;Sharp K;Alfaro-Almagro F;Shi S;Miller KL;Douaud G;Marchini J;Smith SM
通讯作者：
Smith SM
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
4
作者：
Dennis MY;Eichler EE
通讯作者：
Eichler EE
影响因子：
16.6
作者：
Elvsåshagen T;Shadrin A;Frei O;van der Meer D;Bahrami S;Kumar VJ;Smeland O;Westlye LT;Andreassen OA;Kaufmann T
通讯作者：
Kaufmann T
影响因子：
4.4
作者：
de Jong S;Chepelev I;Janson E;Strengman E;van den Berg LH;Veldink JH;Ophoff RA
通讯作者：
Ophoff RA