Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA 92093, USA.
Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA; School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310024, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang 310024, China.
Cell Rep. 2023 Aug 29;42(8):112896. doi: 10.1016/j.celrep.2023.112896. Epub 2023 Jul 27.
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.
染色体倒位对人类大脑形态的影响仍未得到充分探索。我们研究了从 33018 名具有欧洲血统的成年人的基因型中分类的 35 种常见倒位。在与皮质和皮质下形态相关联的研究中，2p22.3、16p11.2 和 17q21.31 的倒位达到了基因组显著水平，其次是 8p23.1 和 6p21.33。17q21.31、8p23.1 和 16p11.2 区域包含 LRRC37、OR7E 和 NPIP 复制基因家族。我们发现，17q21.31MAPT 倒位区域，以含有神经风险而闻名，是常见变异中塑造和模式化皮质的最突出基因座。总的来说，我们观察到倒位方向会减小大脑体积，但 2p22.3 倒位与皮质下体积增加有关，而 8p23.1 倒位与运动皮质增加有关。这些显著的倒位位于神经精神病变位的基因组热点。我们的发现可以推广到 3472 名儿童，并证明倒位是理解人类大脑表型的重要遗传变异。
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