A genome-wide search for linkage to allergic rhinitis in Danish sib-pair families.
A genome-wide search for linkage to allergic rhinitis in Danish sib-pair families.
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DOI：
10.1038/ejhg.2012.46
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发表时间：
2012-09
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影响因子：
--
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中科院分区：
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过敏性鼻炎（AR）是一种多基因、多因素的复杂疾病。对双胞胎的研究发现，基因的贡献是巨大的。我们收集了一个由127个丹麦核心家庭组成的样本，其中至少有两个兄弟姐妹患有AR或过敏性结膜炎，包括540个人（286名儿童和254名父母）。使用424个微卫星标记，对该样本和早期收集的由130个特应性皮炎和其他特应性疾病家庭组成的样本进行了全基因组连锁扫描。先前收集并进行基因分型的第三个兄弟姐妹家庭样本被添加到分析中，将总样本量增加到357个家庭，包括1508个个体。共纳入190个AR家庭。利用Genehunter NPL、Genehunter MOD和Genehunter Imprinting等连锁分析软件，分别获得非参数和参数连锁结果。使用FBAT程序对候选位置snp进行基于家族的关联分析。我们获得了与1p13上一个新的AR位点的全基因组显著连锁，以及分别与1q31-q32和20p12上两个新的区域的提示连锁。候选位点DNND1B/CRB1在1q31处的snp的家族关联分析显示无显著关联，无法解释观察到的连锁信号。在先前报道的三个AR位点（2q14-q23、2q23和12p13）上也获得了连锁的暗示证据，并且在许多其他位点上观察到连锁迹象。可能在2q23和3q28处观察到母体印迹。
Allergic rhinitis (AR) is a complex disorder with a polygenic, multifactorial aetiology. Twin studies have found the genetic contribution to be substantial. We collected and clinically characterised a sample consisting of 127 Danish nuclear families with at least two siblings suffering from AR or allergic conjunctivitis including 540 individuals (286 children and 254 parents). A whole-genome linkage scan, using 424 microsatellite markers, was performed on both this sample and an earlier collected sample consisting of 130 families with atopic dermatitis and other atopic disorders. A third sib-pair family sample, which was previously collected and genotyped, was added to the analysis increasing the total sample size to 357 families consisting of 1508 individuals. In total, 190 families with AR was included. The linkage analysis software Genehunter NPL, Genehunter MOD, and Genehunter Imprinting were used to obtain nonparametric and parametric linkage results. Family-based association analysis of positional candidate SNPs was carried out using the FBAT program. We obtained genome-wide significant linkage to a novel AR locus at 1p13 and suggestive linkage to two novel regions at 1q31-q32 and 20p12, respectively. Family-based association analysis of SNPs in the candidate locus DNND1B/CRB1 at 1q31 showed no significant association and could not explain the linkage signal observed. Suggestive evidence of linkage was also obtained at three AR loci previously reported (2q14-q23, 2q23, and 12p13) and indication of linkage was observed at a number of additional loci. Likely maternal imprinting was observed at 2q23, and possible maternal imprinting at 3q28.
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影响因子：
14.2
作者：
Barnes, KC;Freidhoff, LR;Beaty, TH
通讯作者：
Beaty, TH
影响因子：
5.2
作者：
Horvath, S;Xu, X;Laird, NM
通讯作者：
Laird, NM
影响因子：
5
作者：
Dizier, MH;Bouzigon, E;Annesi-Maesano, I
通讯作者：
Annesi-Maesano, I
影响因子：
30.8
作者：
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通讯作者：
Cookson, WOCM
影响因子：
12.4
作者：
Haagerup, A;Bjerke, T;Kruse, TA
通讯作者：
Kruse, TA