<br>人类和大鼠 BMI 的全基因组关联研究集中于突触、表观基因组和激素信号网络,Cell Reports

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人类和大鼠 BMI 的全基因组关联研究集中于突触、表观基因组和激素信号网络
Cell Reports ( IF 7.5 ) Pub Date : 2023-07-31 , DOI: 10.1016/j.celrep.2023.112873
Sarah N Wright ₁ , Brittany S Leger ₂ , Sara Brin Rosenthal ₃ , Sophie N Liu ₄ , Tongqiu Jia ₄ , Apurva S Chitre ₅ , Oksana Polesskaya ₅ , Katie Holl ₆ , Jianjun Gao ₅ , Riyan Cheng ₅ , Angel Garcia Martinez ₇ , Anthony George ₈ , Alexander F Gileta ₉ , Wenyan Han ₇ , Alesa H Netzley ₁₀ , Christopher P King ₁₁ , Alexander Lamparelli ₁₂ , Connor Martin ₁₁ , Celine L St Pierre ₁₃ , Tengfei Wang ₇ , Hannah Bimschleger ₅ , Jerry Richards ₈ , Keita Ishiwari ₁₄ , Hao Chen ₇ , Shelly B Flagel ₁₅ , Paul Meyer ₁₂ , Terry E Robinson ₁₆ , Leah C Solberg Woods ₁₇ , Jason F Kreisberg ₄ , Trey Ideker ₁₈ , Abraham A Palmer ₁₉

Affiliation

Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA; Program in Bioinformatics and Systems Biology, University of California San Diego, La Jolla, CA 92093, USA.
Department of Psychiatry, University of California San Diego, La Jolla, CA 93093, USA; Program in Biomedical Sciences, University of California San Diego, La Jolla, CA 93093, USA.
Center for Computational Biology & Bioinformatics, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Department of Psychiatry, University of California San Diego, La Jolla, CA 93093, USA.
Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Department of Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Clinical and Research Institute on Addictions, University at Buffalo, Buffalo, NY 14203, USA.
Department of Psychiatry, University of California San Diego, La Jolla, CA 93093, USA; Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
Department of Psychiatry, University of Michigan, Ann Arbor, MI 48109, USA.
Clinical and Research Institute on Addictions, University at Buffalo, Buffalo, NY 14203, USA; Department of Psychology, University at Buffalo, Buffalo, NY 14260, USA.
Department of Psychology, University at Buffalo, Buffalo, NY 14260, USA.
Department of Genetics, Washington University, St. Louis, MO 63110, USA.
Clinical and Research Institute on Addictions, University at Buffalo, Buffalo, NY 14203, USA; Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, NY 14203, USA.
Department of Psychiatry, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Psychology, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA; Institute for Genomic Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Department of Psychiatry, University of California San Diego, La Jolla, CA 93093, USA; Institute for Genomic Medicine, University of California San Diego, La Jolla, CA 92093, USA.

全基因组关联研究（GWAS）中一个令人烦恼的观察是，不同物种的平行分析可能无法识别直系同源基因。在这里，我们证明通过分析分子网络内的共定位可以极大地改善 GWAS 的跨物种翻译。以体重指数 (BMI) 为例，我们发现与人类 BMI 相关的基因与在大鼠中发现的基因缺乏显着一致性。然而，连接这些基因的网络显示出大量重叠，突出了包括突触信号传导、表观遗传修饰和激素调节在内的共同机制。这些网络内的遗传扰动也会导致小鼠出现异常的体重指数表型，这支持了它们在哺乳动物中的广泛保护。其他机制似乎具有物种特异性，包括碳水化合物生物合成（人类）和甘油脂代谢（啮齿动物）。最后，网络共定位还可以识别高度/体长的跨物种收敛。这项研究提出了一个通用范例，用于确定模型物种中测量的表型是否以及如何重现人类生物学。

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更新日期：2023-07-31

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