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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

31卷

期数:

2025年04期

页码:

364-369，384

栏目:

基础医学

出版日期:

2025-07-10

文章信息/Info

Title:

A study on the genetic basis and causality of the association between body mass index and amygdala gray matter volume

文章编号:

1006-8147(2025)04-0364-07

作者:

乐毅鹏; 王秀志; 肖晓啸; 梁猛

（天津医科大学医学技术学院、医学影像学院，天津 300203；天津市功能影像重点实验室，天津 300052）

Author(s):

LE Yipeng;  WANG Xiuzhi;  XIAO Xiaoxiao;  LIANG Meng

（School of Medical Imaging， School of Medical Technology， Tianjin Medical University， Tianjin 300203， China；Tianjin Key Laboratory of Functional Imaging， Tianjin 300052， China）

关键词:

肥胖; 杏仁核灰质体积; 遗传相关性; 多基因风险分数; 孟德尔随机化

Keywords:

obesity;  amygdala gray matter volume;  genetic correlation;  polygenic risk score;  Mendelian randomization

分类号:

R394

DOI:

10.20135/j.issn.1006-8147.2025.04.0364

文献标志码:

A

摘要:

目的：探究双侧杏仁核灰质体积（GMV）与体重指数（BMI）关联性的潜在遗传机制及因果关系。方法：首先，利用3种方法考察了左侧和右侧杏仁核GMV与BMI的遗传相关性：（1）通过对杏仁核GMV和BMI各自的全基因组关联研究（GWAS）结果取交集，检测两者是否存在公共的显著单核苷酸多态性（SNP，P<5×10-8）。（2）基于两者的GWAS结果，使用连锁不平衡分数回归（LDSC）方法计算两者的遗传相关性。（3）通过多基因风险分数（PRS）的跨表型预测方法，考察BMI的PRS是否可预测杏仁核GMV。随后，采用双向两样本孟德尔随机化（MR）探究左侧和右侧杏仁核GMV与BMI之间的因果关系。结果：遗传相关性分析中，方法一结果显示左侧和右侧杏仁核GMV与BMI共存在4个共同的显著SNP，且均定位到载脂蛋白（Apo）E基因或其下游区域。方法二结果显示左侧和右侧杏仁核GMV均与BMI存在负向遗传相关性（左侧：rg=-0.097， P=0.000 5； 右侧：rg=-0.064， P=0.040 5）。方法三结果显示，BMI的PRS可预测左测和右侧杏仁核GMV（左侧：β=-0.023， P=4.87×10-8；右侧：β=-0.026， P=5.67×10-10）。MR分析结果显示，BMI增加会显著降低左侧和右侧杏仁核GMV（左侧：β=-0.116， 95%CI：-2.202

Abstract:

Objective： To investigate the underlying genetic mechanism and the causal relationship between bilateral amygdala gray matter volume（GMV） and body mass index（BMI）. Methods： Firstly， the genetic correlation between GMV of the left and right amygdala and BMI was examined using three approaches： （1）Overlapping significant single-nucleotide polymorphisms （SNPs； P<5×10-8）was detected by intersecting the two sets of significant SNPs obtained from genome-wide association studies（GWAS） for amygdala GMV and BMI. （2）Based on GWAS summary data of the amygdala GMV and BMI， their genetic correlation was calculated using linkage disequilibrium score regression（LDSC）. （3）Using the "cross-trait prediction" method of polygenic risk scores（PRS），whether the PRS of BMI could predict amygdala GMV was investigated. Then bidirectional two sample Mendelian randomization （MR） was used to investigate the causal relationship between left and right amygdala GMV and BMI. Results： In genetic correlation analyses，the first approach identified four significant SNPs shared between left/right amygdala GMV and BMI， and all 4 SNPs were mapped to the apolipoprotein E（ApoE） gene or its downstream regions. The second approach revealed a negative genetic correlation between amyg-dala GMV and BMI for both sides （left：rg= -0.097， P= 0.000 5； right：rg= -0.064， P=0.040 5）. The third approach showed a significant prediction of amygdala GMV based on PRS of BMI for both sides （left： β=-0.023， P=4.87×10-8； right： β= -0.026， P=5.67×10-10）. The MR results showed that higher BMI significantly reduced the GMV of the left and right amygdala（left： β=-0.116， 95%CI： -2.202 - -0.029，P=0.009；right： β=-0.136， 95%CI： -0.217 - -0.056， P=0.001）， whereas the effects of left or right amygdala GMV on BMI were not significant. Conclusion： Bilateral amygdala GMV and BMI has a significant negative genetic correlation. Obesity is a risk factor for the reduction of amygdala GMV.

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备注/Memo

备注/Memo:

作者简介:乐毅鹏（2000-），男，硕士在读，研究方向：影像遗传学；通信作者：梁猛，E-mail：liangmeng@tmu.edu.cm。

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更新日期/Last Update: 2025-07-10