A PheWAS approach in studying HLA-DRB1*1501.
A PheWAS approach in studying HLA-DRB1*1501.
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DOI：
10.1038/gene.2013.2
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发表时间：
2013-04
影响因子：
5
通讯作者：
Brilliant, M. H.
中科院分区：
文献类型：
--
作者：
Hebbring, S. J.;Schrodi, S. J.;Ye, Z.;Zhou, Z.;Page, D.;Brilliant, M. H.
HLA-DRB1编码一个主要的组织相容性复合体II类细胞表面受体。该基因及其周围的遗传变异与许多自身免疫性疾病有关。最值得注意的是，HLA-DRB1*1501单倍型与多发性硬化症之间的关联已被确定。利用马什菲尔德诊所个性化医学研究项目中的电子健康记录和4235名个体，一项名为全表型关联研究（PheWAS）的反向基因筛选测试了rs3135388基因型（标记HLA-DRB1*1501）与4841种表型的关联。正如预期的那样，HLA-DRB1*1501与多发性硬化症相关（ICD9 340， P=0.023），而与酒精性肝硬化相关性最强（ICD9 571.2， P=0.00011）。HLA-DRB1*1501还显示与红斑状况（icd995， P=0.0054）和呼吸和胸内器官良性肿瘤（icd9212， P=0.042）相关，与先前的发现重复。这项研究不仅建立在PheWAS方法的可行性/实用性上，代表了PheWAS的首次外部验证，而且可能还证明了与HLA-DRB1*1501位点相关的复杂病因。
HLA-DRB1 codes for a major histocompatibility complex class II cell surface receptor. Genetic variants in and around this gene have been linked to numerous autoimmune diseases. Most notably, an association between HLA-DRB1*1501 haplotype and multiple sclerosis has been defined. Utilizing electronic health records and 4235 individuals within Marshfield Clinic’s Personalized Medicine Research Project, a reverse genetic screen coined Phenome Wide Association Study (PheWAS) tested association of rs3135388 genotype (tagging HLA-DRB1*1501) with 4841 phenotypes. As expected, HLA-DRB1*1501 was associated with multiple sclerosis (ICD9 340, P=0.023), while the strongest association was with alcohol-induced cirrhosis of the liver (ICD9 571.2, P=0.00011). HLA-DRB1*1501 also demonstrated association with erythematous conditions (ICD9 695, P=0.0054) and benign neoplasms of the respiratory and intrathoracic organs (ICD9 212, P=0.042), replicating previous findings. This study not only builds on the feasibility/utility of the PheWAS approach, represents the first external validation of a PheWAS, but may also demonstrate the complex etiologies associated with the HLA-DRB1*1501 loci.
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