Genome-wide association analyses identify new loci influencing intraocular pressure
Genome-wide association analyses identify new loci influencing intraocular pressure
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DOI：
10.1093/hmg/ddy111
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发表时间：
2018-06-15
影响因子：
3.5
通讯作者：
Kim, Heejin
中科院分区：
文献类型：
--
作者：
Gao, X. Raymond;Huang, Hua;Kim, Heejin
眼压升高是青光眼的重要危险因素，青光眼是全球不可逆性失明的主要原因。虽然之前的研究已经发现了许多与眼压相关的遗传变异，但这些基因座只解释了眼压遗传性的一小部分。最近建立的生物库已经产生了大量的数据，使得能够识别复杂性状的剩余遗传力。在这里，我们描述了迄今为止最大的眼压全基因组关联研究，研究对象是来自英国生物库的欧洲血统的参与者。我们确定了671个与眼压显著相关的直接基因分型变异(P<；5x10(-8))。除了103个新基因座外，排名最靠前的新眼压基因是Lmx1b、NR1H3、MADD和SEPT9。我们在外部人群中复制了这些发现，并检查了这些基因座的多效性。这些发现不仅加深了我们对眼压遗传结构的理解，也为青光眼的生物学过程提供了新的线索。
Elevated intraocular pressure (IOP) is a significant risk factor for glaucoma, the leading cause of irreversible blindness worldwide. While previous studies have identified numerous genetic variants associated with IOP, these loci only explain a fraction of IOP heritability. Recently established of biobank repositories have resulted in large amounts of data, enabling the identification of the remaining heritability for complex traits. Here, we describe the largest genome-wide association study of IOP to date using participants of European ancestry from the UK Biobank. We identified 671 directly genotyped variants that are significantly associated with IOP (P< 5 x 10(-8)). In addition to 103 novel loci, the top ranked novel IOP genes are LMX1B, NR1H3, MADD and SEPT9. We replicated these findings in an external population and examined the pleiotropic nature of these loci. These discoveries not only further our understanding of the genetic architecture of IOP, but also shed new light on the biological processes underlying glaucoma.