Genome-wide association analysis reveals variants on chromosome 19 that contribute to childhood risk of chronic otitis media with effusion.
Genome-wide association analysis reveals variants on chromosome 19 that contribute to childhood risk of chronic otitis media with effusion.
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DOI：
10.1038/srep33240
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发表时间：
2016-09-16
影响因子：
4.6
通讯作者：
Mattila PS
中科院分区：
文献类型：
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作者：
Einarsdottir E;Hafrén L;Leinonen E;Bhutta MF;Kentala E;Kere J;Mattila PS
为了确定儿童中耳炎（OM）的遗传危险因素，对芬兰受试者，829名受影响儿童和2118名随机选择的对照组进行了全基因组关联研究。最重要和验证的发现是与19号染色体上的80 kb区域的关联。它包括变体rs 16974263（P = 1.77 × 10−7，OR = 1.59），rs268662（P = 1.564 × 10−6，OR = 1.54）和rs 4150992（P = 3.37 × 10−6，OR = 1.52），并携带基因PLD 3、SERTAD 1、SERTAD 3、HIPK 4、PRX和BLVRB，均处于强连锁不平衡状态。在对512例慢性渗出性中耳炎患者的亚表型分析中，一个标记物达到了全基因组显著性（rs 16974263，P = 2.92 × 10−8）。在一个由4860名受试者组成的英国家族队列中，与该基因座的关联得到了证实，但关联信号方向相反（rs 16974263，P = 3.21 × 10−4，OR = 0.72; rs 4150992，P = 1.62 × 10−4，OR = 0.71）。因此，我们假设，这一地区是重要的COME风险在芬兰和英国的人口，虽然精确的风险变异或单倍型背景仍不清楚。我们的研究表明，19号染色体上的确定区域包括一个新的和以前未知的风险位点OM。
To identify genetic risk factors of childhood otitis media (OM), a genome-wide association study was performed on Finnish subjects, 829 affected children, and 2118 randomly selected controls. The most significant and validated finding was an association with an 80 kb region on chromosome 19. It includes the variants rs16974263 (P = 1.77 × 10−7, OR = 1.59), rs268662 (P = 1.564 × 10−6, OR = 1.54), and rs4150992 (P = 3.37 × 10−6, OR = 1.52), and harbors the genes PLD3, SERTAD1, SERTAD3, HIPK4, PRX, and BLVRB, all in strong linkage disequilibrium. In a sub-phenotype analysis of the 512 patients with chronic otitis media with effusion, one marker reached genome-wide significance (rs16974263, P = 2.92 × 10−8). The association to this locus was confirmed but with an association signal in the opposite direction, in a UK family cohort of 4860 subjects (rs16974263, P = 3.21 × 10−4, OR = 0.72; rs4150992, P = 1.62 × 10−4, OR = 0.71). Thus we hypothesize that this region is important for COME risk in both the Finnish and UK populations, although the precise risk variants or haplotype background remain unclear. Our study suggests that the identified region on chromosome 19 includes a novel and previously uncharacterized risk locus for OM.