The Evolutionary History of Common Genetic Variants Influencing Human Cortical Surface Area.
The Evolutionary History of Common Genetic Variants Influencing Human Cortical Surface Area.
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DOI：
10.1093/cercor/bhaa327
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发表时间：
2021-03-05
期刊：
影响因子：
--
通讯作者：
Stein JL
中科院分区：
文献类型：
--
作者：
Tilot AK;Khramtsova EA;Liang D;Grasby KL;Jahanshad N;Painter J;Colodro-Conde L;Bralten J;Hibar DP;Lind PA;Liu S;Brotman SM;Thompson PM;Medland SE;Macciardi F;Stranger BE;Davis LK;Fisher SE;Stein JL
大脑结构的变化沿着导致现代智人的血统，有助于我们独特的认知和社会能力。然而，影响神经解剖学关键方面的进化相关分子变异在很大程度上是未知的。在这里，我们整合了不同时间尺度的基因组进化注释与大规模神经影像遗传筛查的常见变异关联。我们发现，在过去的2000-3000年中，具有最近正多基因选择证据的等位基因与整个皮层以及特定区域的表面积（SA）增加有关，包括那些参与口语和视觉处理的区域。因此，多基因选择性压力影响特定皮层区域的结构，即使在相对较近的时间尺度。此外，人类获得的增强子在产前皮质中的活性与出生后的全球SA相关。我们表明，这种变化调制的功能的调控元件的发育相关的转录因子HEY 2在人类神经祖细胞，并与结构变化在额叶皮层下部。这些结果表明，在产前皮质发育过程中活跃的非编码基因组区域参与了人脑结构的进化，并确定了影响现代人脑结构的新调控元件和基因。
Structural brain changes along the lineage leading to modern Homo sapiens contributed to our distinctive cognitive and social abilities. However, the evolutionarily relevant molecular variants impacting key aspects of neuroanatomy are largely unknown. Here, we integrate evolutionary annotations of the genome at diverse timescales with common variant associations from large-scale neuroimaging genetic screens. We find that alleles with evidence of recent positive polygenic selection over the past 2000–3000 years are associated with increased surface area (SA) of the entire cortex, as well as specific regions, including those involved in spoken language and visual processing. Therefore, polygenic selective pressures impact the structure of specific cortical areas even over relatively recent timescales. Moreover, common sequence variation within human gained enhancers active in the prenatal cortex is associated with postnatal global SA. We show that such variation modulates the function of a regulatory element of the developmentally relevant transcription factor HEY2 in human neural progenitor cells and is associated with structural changes in the inferior frontal cortex. These results indicate that non-coding genomic regions active during prenatal cortical development are involved in the evolution of human brain structure and identify novel regulatory elements and genes impacting modern human brain structure.
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影响因子：
64.5
作者：
de la Torre-Ubieta L;Stein JL;Won H;Opland CK;Liang D;Lu D;Geschwind DH
通讯作者：
Geschwind DH
影响因子：
16.2
作者：
Geschwind DH;Rakic P
通讯作者：
Rakic P
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：
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：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL