The imprinted DLK1-MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes.
The imprinted DLK1-MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes.
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对常见疾病易感基因座的全基因组关联研究已经取得了巨大的成功，到目前为止已报道了300多个可重复相关的基因座，但或许令人惊讶的是，尚未提供令人信服的证据证明任何易感基因座受起源父母的影响。我们使用补偿来扩展现有的全基因组关联数据集，并在此报告了位于rs941576的强有力的证据，表明在染色体14q32.2的印迹区域，父系遗传1型糖尿病的风险(T1D，父系与母系遗传的等位基因效应比率=0.75，95%CI=0.71-0.79)，该区域包含一个功能候选基因DLK1。我们的Meta分析还提供了位于染色体19p13.2的T1D基因座的全基因组意义上的支持，其中TYK2基因中标记rs2304256(OR=0.86，95%CI=0.82-0.90)的关联度最高，该基因曾与系统性红斑狼疮相关。
Genomewide association studies to map common disease susceptibility loci have been hugely successful with over 300 reproducibly associated loci reported to date, but, perhaps surprisingly, have not yet provided convincing evidence for any susceptibility locus subject to parent of origin effects. We used imputation to extend existing genomewide association datasets and here report robust evidence, at rs941576, for paternally inherited risk of type 1 diabetes (T1D, ratio of allelic effects for paternal vs maternal transmissions = 0.75, 95%CI=0.71–0.79), in the imprinted region of chromosome 14q32.2, which contains a functional candidate gene, DLK1. Our meta-analysis also provided support at genomewide significance for a T1D locus at chromosome 19p13.2, with the highest association at marker rs2304256 (OR=0.86, 95%CI=0.82–0.90) in the TYK2 gene, which has previously associated with systemic lupus erythematosus.