Brain Magnetic Resonance Imaging Phenome-Wide Association Study With Metal Transporter Gene SLC39A8.
Brain Magnetic Resonance Imaging Phenome-Wide Association Study With Metal Transporter Gene SLC39A8.
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DOI：
10.3389/fgene.2021.647946
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发表时间：
2021
影响因子：
3.7
通讯作者：
Chowanadisai W
中科院分区：
文献类型：
--
作者：
Hermann ER;Chambers E;Davis DN;Montgomery MR;Lin D;Chowanadisai W
SLC39A8基因编码二价金属转运蛋白ZIP8。SLC39A8与包括大脑在内的多个组织的多效性效应有关。我们确定了与SLC39A8相关的不同脑磁共振成像(MRI)表型。我们使用了表观范围的关联研究方法，然后是联合关联分析和条件关联分析。使用来自成年英国生物库参与者的脑MRI全基因组关联研究的汇总统计数据集，我们系统地选择了与SLC39A8遗传基因座500kb内的单核苷酸多态(SNPs)相关的所有脑MRI表型。对于所有显著的脑MRI表型，我们使用GCTA-COJO来确定独立关联信号的数量，并确定每种脑MRI表型的索引SNP。用LDPair验证了脑表型与多个独立信号的连锁平衡。我们确定了24种脑MRI表型，这些表型因MRI类型和脑区域而异，并包含与SLC39A8基因座相关的SNP。ZIP8错义多态rs13107325与22个脑MRI表型相关。英国生物库数据集中出现的罕见ZIP8变异与6种脑MRI表型相关，这些表型也与rs13107325相关。在24个数据集中，GCTA-COJO鉴定到另外4个关联信号，并利用LDPair确认它们与rs13107325处于连锁平衡。这些额外的关联信号代表除了rs13107325之外的新的可能的致病SNPs。这项研究揭示了微量矿物质运输基因SLC39A8的遗传变异如何与大脑结构差异有关，并可能影响大脑发育和神经系统功能。
The SLC39A8 gene encodes a divalent metal transporter, ZIP8. SLC39A8 is associated with pleiotropic effects across multiple tissues, including the brain. We determine the different brain magnetic resonance imaging (MRI) phenotypes associated with SLC39A8. We used a phenome-wide association study approach followed by joint and conditional association analysis. Using the summary statistics datasets from a brain MRI genome-wide association study on adult United Kingdom (UK) Biobank participants, we systematically selected all brain MRI phenotypes associated with single-nucleotide polymorphisms (SNPs) within 500 kb of the SLC39A8 genetic locus. For all significant brain MRI phenotypes, we used GCTA-COJO to determine the number of independent association signals and identify index SNPs for each brain MRI phenotype. Linkage equilibrium for brain phenotypes with multiple independent signals was confirmed by LDpair. We identified 24 brain MRI phenotypes that vary due to MRI type and brain region and contain a SNP associated with the SLC39A8 locus. Missense ZIP8 polymorphism rs13107325 was associated with 22 brain MRI phenotypes. Rare ZIP8 variants present in a published UK Biobank dataset are associated with 6 brain MRI phenotypes also linked to rs13107325. Among the 24 datasets, an additional 4 association signals were identified by GCTA-COJO and confirmed to be in linkage equilibrium with rs13107325 using LDpair. These additional association signals represent new probable causative SNPs in addition to rs13107325. This study provides leads into how genetic variation in SLC39A8, a trace mineral transport gene, is linked to brain structure differences and may affect brain development and nervous system function.
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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：
16.6
作者：
Haller G;McCall K;Jenkitkasemwong S;Sadler B;Antunes L;Nikolov M;Whittle J;Upshaw Z;Shin J;Baschal E;Cruchaga C;Harms M;Raggio C;Morcuende JA;Giampietro P;Miller NH;Wise C;Gray RS;Solnica-Krezel L;Knutson M;Dobbs MB;Gurnett CA
通讯作者：
Gurnett CA
影响因子：
7
作者：
Boyle AP;Hong EL;Hariharan M;Cheng Y;Schaub MA;Kasowski M;Karczewski KJ;Park J;Hitz BC;Weng S;Cherry JM;Snyder M
通讯作者：
Snyder M
影响因子：
3.7
作者：
Chowanadisai W
通讯作者：
Chowanadisai W
DOI：
10.1073/pnas.1222142110
发表时间：
2013-06-11
影响因子：
11.1
作者：
Chowanadisai, Winyoo;Graham, David M.;Messerli, Mark A.
通讯作者：
Messerli, Mark A.