Heritability of non-HLA genetics in coeliac disease: a population-based study in 107 000 twins
Heritability of non-HLA genetics in coeliac disease: a population-based study in 107 000 twins
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DOI：
10.1136/gutjnl-2016-311713
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发表时间：
2016-11-01
期刊：
影响因子：
24.5
通讯作者：
Ludvigsson, Jonas F.
中科院分区：
文献类型：
--
作者：
Kuja-Halkola, Ralf;Lebwohl, Benjamin;Ludvigsson, Jonas F.
背景与目的乳糜泻（CD）患者几乎100%携带人类白细胞抗原（HLA）DQ 2/DQ 8等位基因。然而，早期的研究未能考虑HLA系统时，估计遗传力在CD，从而违反了遗传力分析的基本假设。我们研究了遗传性的CD在一个大的人口为基础的样本的双胞胎，考虑HLA.Design在人口代表性的样本107 912双胞胎，我们确定了个人与CD（等于绒毛萎缩）通过活检报告从所有瑞典病理部门。我们计算了同卵（MZ）和异卵（DZ）双胞胎对的一致率和四项相关。此外，我们估计CD的遗传性，首先严格从观察到的数据，然后非HLA遗传性，代表的遗传性的所有遗传因素，除了HLA位点，使用的方法，规避违反基本的hypothesis.Results我们确定了513双胞胎诊断CD（患病率0.48%）。MZ对的一致率（0.49）高于DZ对（0.10），四项相关性（MZ对0.89 vs DZ对0.51）也是如此。CD的遗传度为75%（95%CI 55%~ 96%）。非HLA遗传性略有减弱，68%（95%CI 40%至96%），共享（17%）和非共享（15%）的环境因素解释其余的变异CD。结论CD的特点是高遗传性，但我们的研究还表明，非共享的环境因素可能是CD发展的重要性。HLA似乎只有适度的影响，遗传估计。
Background and objective Almost 100% individuals with coeliac disease (CD) are carriers of the human leucocyte antigen (HLA) DQ2/DQ8 alleles. Earlier studies have, however, failed to consider the HLA system when estimating heritability in CD, thus violating an underlying assumption of heritability analysis. We examined the heritability of CD in a large population-based sample of twins, considering HLA.Design In a population-representative sample of 107 912 twins, we identified individuals with CD (equal to villous atrophy) through biopsy reports from all Swedish pathology departments. We calculated concordance rates and tetrachoric correlations for monozygotic (MZ) and dizygotic (DZ) twin pairs. Further, we estimated heritability of CD, first strictly from observed data, and then the non-HLA heritability, representing the heritability of all genetic factors except the HLA locus, using an approach that circumvent the violation of underlying assumptions.Results We identified 513 twins with a diagnosis of CD (prevalence 0.48%). Concordance rates were higher in MZ pairs (0.49) than in DZ pairs (0.10), as were tetrachoric correlations (0.89 in MZ vs 0.51 in DZ pairs). The heritability of CD was 75% (95% CI 55% to 96%). The non-HLA heritability was slightly attenuated, 68% (95% CI 40% to 96%), with shared (17%) and nonshared (15%) environmental factors explaining the remaining variability of CD.Conclusions CD is characterised by a high heritability, but our study also suggests that non-shared environmental factors may be of importance to CD development. HLA seems to have only moderate impact on heritability estimates.