A genome-wide association study of bipolar disorder with comorbid eating disorder replicates the SOX2-OT region.
A genome-wide association study of bipolar disorder with comorbid eating disorder replicates the SOX2-OT region.
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DOI：
10.1016/j.jad.2015.09.029
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发表时间：
2016-01-01
影响因子：
6.6
通讯作者：
Greenwood TA
中科院分区：
文献类型：
--
作者：
Liu X;Bipolar Genome Study (BiGS);Kelsoe JR;Greenwood TA
双相情感障碍是一种异质性情绪障碍，与几种重要的临床合并症相关，例如饮食失调。这种临床异质性使得导致双相情感障碍易感性的遗传变异的识别变得复杂。在这里，我们研究饮食失调的共病作为双相情感障碍的亚表型，以确定这两种疾病常见和独特的遗传变异。我们进行了全基因组关联分析，将 184 名患有饮食失调共病的双相情感障碍受试者与 1,370 名对照者和 2,006 名仅来自双相情感障碍基因组研究 (BiGS) 的双相情感障碍受试者进行了对比。最显着的全基因组发现是在SOX2-OT（rs4854912 的p=8.9×10−8）内观察到患有饮食失调的双相情感障碍患者与对照组，在染色体3q26.33 上的邻近FXR1 基因（rs1805576 的p=1.2×10−6）中存在次峰。该区域也是仅病例分析中最突出的发现（分别为 p=3.5×10−7 和 4.3×10−6）。还鉴定了几个含有参与神经发育和神经保护过程的基因的感兴趣区域。虽然我们的主要发现并没有完全达到全基因组的显着性，可能是由于样本量相对有限，但这些结果可以被视为最近在一个大队列中进行的饮食失调研究的复制。这些发现复制了 SOX2-OT 与饮食失调的先前关联，并广泛支持神经发育/神经保护机制参与这两种疾病的病理生理学。他们进一步表明，双相情感障碍的不同临床表现可能反映了不同的遗传贡献，并主张临床亚表型在识别导致疾病的其他分子途径方面的实用性。
Bipolar disorder is a heterogeneous mood disorder associated with several important clinical comorbidities, such as eating disorders. This clinical heterogeneity complicates the identification of genetic variants contributing to bipolar susceptibility. Here we investigate comorbidity of eating disorders as a subphenotype of bipolar disorder to identify genetic variation that is common and unique to both disorders. We performed a genome-wide association analysis contrasting 184 bipolar subjects with eating disorder comorbidity against both 1,370 controls and 2,006 subjects with bipolar disorder only from the Bipolar Genome Study (BiGS). The most significant genome-wide finding was observed bipolar with comorbid eating disorder vs. controls within SOX2-OT (p=8.9×10−8 for rs4854912) with a secondary peak in the adjacent FXR1 gene (p=1.2×10−6 for rs1805576) on chromosome 3q26.33. This region was also the most prominent finding in the case-only analysis (p=3.5×10−7 and 4.3×10−6, respectively). Several regions of interest containing genes involved in neurodevelopment and neuroprotection processes were also identified. While our primary finding did not quite reach genome-wide significance, likely due to the relatively limited sample size, these results can be viewed as a replication of a recent study of eating disorders in a large cohort. These findings replicate the prior association of SOX2-OT with eating disorders and broadly support the involvement of neurodevelopmental/neuroprotective mechanisms in the pathophysiology of both disorders. They further suggest that different clinical manifestations of bipolar disorder may reflect differential genetic contributions and argue for the utility of clinical subphenotypes in identifying additional molecular pathways leading to illness.