A genome-wide association study of intra-ocular pressure suggests a novel association in the gene FAM125B in the TwinsUK cohort.
A genome-wide association study of intra-ocular pressure suggests a novel association in the gene FAM125B in the TwinsUK cohort.
复制标题
DOI：
10.1093/hmg/ddu050
复制
发表时间：
2014-06-15
影响因子：
3.5
通讯作者：
Hammond C
中科院分区：
文献类型：
--
作者：
Nag A;Venturini C;Small KS;International Glaucoma Genetics Consortium;Young TL;Viswanathan AC;Mackey DA;Hysi PG;Hammond C
青光眼是世界上导致失明的主要原因。迄今为止，与青光眼相关的常见遗传变异只能解释其遗传性的一小部分。我们对眼内压（IOP）（青光眼的潜在内表型）进行了全基因组关联研究。该研究的发现阶段是在 TwinsUK 队列（N = 2774）中进行的，分析 IOP 与归因于 HapMap2 的单核苷酸多态性 (SNP) 之间的关联。结果在 12 个欧洲血统的独立复制队列（合并 N = 22 789）中得到验证，这些队列是国际青光眼遗传学联盟的一部分。使用多组织人类表达资源 (MuTHER) 研究的数据对显着相关的 SNP 进行表达数量性状位点 (eQTL) 分析。在 TwinsUK 队列中，IOP 与 FAM125B 基因基因组序列中 9q33.3 处的许多 SNP 显着相关（rs2286885 的 P = 3.48 × 10−8，这是该位点上最显着相关的 SNP）。 12 个队列的复合小组中的独立复制揭示了一致的效应方向和显着关联（对于固定效应荟萃分析，P = 0.003）。对于针对 FAM125B 基因编码区的探针之一，观察到了 rs2286885 的 eQTL 效应的暗示证据。该基因编码参与囊泡运输过程的膜复合物的一个组成部分，其功能类似于先前与原发性开角型青光眼相关的 Caveolin 基因（CAV1 和 CAV2）。这项研究表明 TwinsUK 队列中 FAM125B 中的 SNP 与 IOP 之间存在新的关联，但需要进一步研究来阐明该基因在青光眼中的功能作用。
Glaucoma is a major cause of blindness in the world. To date, common genetic variants associated with glaucoma only explain a small proportion of its heritability. We performed a genome-wide association study of intra-ocular pressure (IOP), an underlying endophenotype for glaucoma. The discovery phase of the study was carried out in the TwinsUK cohort (N = 2774) analyzing association between IOP and single nucleotide polymorphisms (SNPs) imputed to HapMap2. The results were validated in 12 independent replication cohorts of European ancestry (combined N = 22 789) that were a part of the International Glaucoma Genetics Consortium. Expression quantitative trait locus (eQTL) analyses of the significantly associated SNPs were performed using data from the Multiple Tissue Human Expression Resource (MuTHER) Study. In the TwinsUK cohort, IOP was significantly associated with a number of SNPs at 9q33.3 (P = 3.48 × 10−8 for rs2286885, the most significantly associated SNP at this locus), within the genomic sequence of the FAM125B gene. Independent replication in a composite panel of 12 cohorts revealed consistent direction of effect and significant association (P = 0.003, for fixed-effect meta-analysis). Suggestive evidence for an eQTL effect of rs2286885 was observed for one of the probes targeting the coding region of the FAM125B gene. This gene codes for a component of a membrane complex involved in vesicular trafficking process, a function similar to that of the Caveolin genes (CAV1 and CAV2) which have previously been associated with primary open-angle glaucoma. This study suggests a novel association between SNPs in FAM125B and IOP in the TwinsUK cohort, though further studies to elucidate the functional role of this gene in glaucoma are necessary.
登录
查看更多内容
影响因子：
6.6
作者：
Wray NR;Visscher PM
通讯作者：
Visscher PM
影响因子：
4.5
作者：
Ramdas WD;van Koolwijk LM;Ikram MK;Jansonius NM;de Jong PT;Bergen AA;Isaacs A;Amin N;Aulchenko YS;Wolfs RC;Hofman A;Rivadeneira F;Oostra BA;Uitterlinden AG;Hysi P;Hammond CJ;Lemij HG;Vingerling JR;Klaver CC;van Duijn CM
通讯作者：
van Duijn CM
影响因子：
13.7
作者：
Foster, PJ;Baasanhu, J;Johnson, GJ
通讯作者：
Johnson, GJ
影响因子：
3.4
作者：
Pedrigi, Ryan M.;Simon, David;Overby, Darryl R.
通讯作者：
Overby, Darryl R.
影响因子：
13.7
作者：
Leske, M. Cristina;Wu, S. Y.;Hennis, A.
通讯作者：
Hennis, A.