Genome-wide Association Study of Anthropometric Traits in Korcula Island, Croatia
Genome-wide Association Study of Anthropometric Traits in Korcula Island, Croatia
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DOI：
10.3325/cmj.2009.50.7
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发表时间：
2009-02-01
影响因子：
1.9
通讯作者：
Rudan, Igor
中科院分区：
文献类型：
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作者：
Polasek, Ozren;Marusic, Ana;Rudan, Igor
目的利用全基因组关联研究确定身高、体重、体重指数、臂围、腰围和臀围6个人体测量性状的遗传变异。方法2007年在克罗地亚科尔库拉岛与世隔绝的人群中进行了898名成年受试者的基因流行病学研究。人体测量遵循国际公认的标准程序。结果共检测到11个单核苷酸多态(SNP)，其中1个SNP(锌指蛋白498基因中的rs7792939)与体重、臀围、臂围相关(P=3.59~5.73 x 10(-6))，1个(Ss157350)基因(Sgcd)同时与臂围和臀围相关(P=3.70~6.08 x 10(-6))。CRIM1基因和IIGA1基因的变异也与臂围有关(分别为7.82和9.68×10(-6))，代表了有趣的候选功能。CRIM1是一种调控骨形态发生蛋白向细胞表面输送的基因，IIGA1参与调控间充质干细胞的增殖和软骨生成。其他关联涉及SEZ6L2和MAX基因与腰围、XTP6与臂围、AMPA1/GRIA1与身高之间的关联。结论尽管在独立多重测试的假设下，已报道的关联达到全基因组意义的正式阈值，但这两个变量与一组人体测量学性状之间的关联的一致性使CRIM1和ITGA1对进一步的复制和功能跟踪非常感兴趣。隔离群体中使用的标记之间的连锁不平衡增加使得正式意义阈值过于严格，隔离群体中等位基因频率的变化可能有助于识别在大型远交群体中不易识别的变异。
Aim To identify genetic variants underlying six anthropometric traits: body height, body weight, body mass index, brachial circumference, waist circumference, and hip circumference, using a genome-wide association study.Methods The study was carried out in the isolated population of the island of Korcula, Croatia, with 898 adult examinees who participated in the larger DNA-based genetic epidemiological study in 2007. Anthropometric measurements followed standard internationally accepted procedures. Examinees were genotyped using HumanHap 370CNV chip by Illumina, with a genome-wide scan containing 316 730 single nucleotide polymorphisms (SNP).Results A total of 11 SNPs were associated with the investigated traits at the level of P < 10(-5), with one SNP (rs7792939 in gene zinc finger protein 498, ZNF498) associated with body weight, hip circumference, and brachial circumference (P = 3.59-5.73 x 10(-6)), and another one (rs157350 in gene delta-sarcoglycan, SGCD) with both brachial and hip circumference (P = 3.70-6.08 x 10(-6)). Variants in CRIM1, a gene regulating delivery of bone morphogenetic proteins to the cell surface, and IIGA1, involved in the regulation of mesenchymal stem cell proliferation and cartilage production, were also associated with brachial circumference (P = 7.82 and 9.68 x 10(-6), respectively) and represent interesting functional candidates. Other associations involved those between genes SEZ6L2 and MAX and waist circumference, XTP6 and brachial circumference, and AMPA1/GRIA1 and height.Conclusion Although the study was underpowered for the reported associations to reach formal threshold of genome-wide significance under the assumption of independent multiple testing, the consistency of association between the 2 variants and a set of anthropometric traits makes CRIM1 and ITGA1 highly interesting for further replication and functional follow-up. Increased linkage disequilibrium between the used markers in an isolated population makes the formal significance threshold overly stringent, and changed allele frequencies in isolate population may contribute to identifying variants that would not be easily identified in large outbred populations.