GWAS Findings for Human Iris Patterns: Associations with Variants in Genes that Influence Normal Neuronal Pattern Development
GWAS Findings for Human Iris Patterns: Associations with Variants in Genes that Influence Normal Neuronal Pattern Development
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DOI：
10.1016/j.ajhg.2011.07.011
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发表时间：
2011-08-12
影响因子：
9.8
通讯作者：
Medland, Sarah E.
中科院分区：
文献类型：
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作者：
Larsson, Mats;Duffy, David L.;Medland, Sarah E.
人类的虹膜模式是高度可变的。这种变异的起源在虹膜相关眼病和法医学的研究中以及从胚胎发育的角度来看与神经发育的基本过程可能存在关系方面都很有意义。我们已经进行了全基因组关联扫描的四个虹膜特征（隐窝频率，皱纹收缩，瞳孔周围色素环的存在，和痣的数量）在三个澳大利亚样本的欧洲血统。这一发现（n = 2121）和复制（n = 499和73）样本显示了（1）隐窝频率和轴突导向基因SEMA 3A变异之间的关联证据（p = 6.6 x 10（-11）），（2）细胞骨架基因TRAF 3 IP 1内的沟收缩和变体（p = 2.3 × 10 ~（-12））;（3）色素环和已知色素基因SLC 24 A4的变体（p = 7.6 × 10 ~（-21））。这些重复的发现分别占这些虹膜特征方差的约1.5%-3%。由于SEMA 3A和TRAFIP 1都参与了控制神经发生、神经迁移和突触发生的途径，我们还研究了这些基因增强的证据，发现了隐窝和沟的富集。这些发现表明，参与正常神经元模式发育的基因也可能影响人类虹膜的组织结构。
Human iris patterns are highly variable. The origins of this variation are of interest in the study of iris-related eye diseases and forensics, as well as from an embryological developmental perspective, with regard to their possible relationship to fundamental processes of neurodevelopment. We have performed genome-wide association scans on four iris characteristics (crypt frequency, furrow contractions, presence of peripupillary pigmented ring, and number of nevi) in three Australian samples of European descent. Both the discovery (n = 2121) and replication (n = 499 and 73) samples showed evidence for association between (1) crypt frequency and variants in the axonal guidance gene SEMA3A (p = 6.6 x 10(-11)), (2) furrow contractions and variants within the cytoskeleton gene TRAF3IP1 (p = 2.3 x 10(-12)), and (3) the pigmented ring and variants in the well-known pigmentation gene SLC24A4 (p = 7.6 x 10(-21)). These replicated findings individually accounted for around 1.5%-3% of the variance for these iris characteristics. Because both SEMA3A and TRAFIP1 are implicated in pathways that control neurogenesis, neural migration, and synaptogenesis, we also examined the evidence of enhancement among such genes, finding enrichment for crypts and furrows. These findings suggest that genes involved in normal neuronal pattern development may also influence tissue structures in the human iris.