A genome-wide association study of bipolar disorder and comorbid migraine.
A genome-wide association study of bipolar disorder and comorbid migraine.
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DOI：
10.1111/j.1601-183x.2010.00601.x
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发表时间：
2010-10
期刊：
影响因子：
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通讯作者：
Kelsoe JR
中科院分区：
文献类型：
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作者：
Oedegaard KJ;Greenwood TA;Johansson S;Jacobsen KK;Halmoy A;Fasmer OB;Akiskal HS;Bipolar Genome Study (BiGS);Haavik J;Kelsoe JR
偏头痛和双相情感障碍(BPAD)都是复杂的表型，具有重要的遗传和非遗传成分。流行病学和临床研究表明，偏头痛和BPAD之间存在高度的共同发病，并且在许多全基因组范围的连锁研究中显示了重叠的连锁区域。为了确定BPAD/偏头痛表型的易感因素，我们对通过NIMH双相情感障碍遗传学倡议收集的1001例双相情感障碍患者进行了全基因组关联研究(GWAS)，并作为遗传关联信息网络(Gain)的一部分，在1M个SNPs上进行了基因分型。我们比较了699例无头痛的BPAD患者和56例医生诊断为偏头痛的BPAD患者。在包含未鉴定基因KIAA0564的317kb区域的几个SNP中发现了最有力的关联证据(例如rs9566845(OR=4.98(95%CI：2.6-9.48，p=7.7×10−8)和rs9566867(p=8.2×10−8))。虽然用Fisher‘s精确检验(偏头痛病例数少)，rs9566845p=1.4×10−5和rs9566867p=1.5×10−5的显著性水平显著降低，但这一区域仍是最显著的发现。此外，标记rs9566845在一个独立的挪威成人ADHD患者样本中被发现与偏头痛相关，OR=2.42(1.18-4.97)，p=0.013。这是第一个检查双相情感障碍和偏头痛共病患者的GWAS。这些数据表明，KIAA0564基因区域的遗传变异可能在BPAD和ADHD患者的亚组中易患偏头痛。
Both migraine and Bipolar Disorder (BPAD) are complex phenotypes with significant genetic and non-genetic components. Epidemiological and clinical studies have demonstrated a high degree of co-morbidity between migraine and BPAD, and overlapping regions of linkage have been shown in numerous genome-wide linkage studies. To identify susceptibility factors for the BPAD/migraine phenotype, we conducted a genome-wide association study (GWAS) in 1001 cases with bipolar disorder collected through the NIMH Genetics Initiative for Bipolar Disorder and genotyped at 1M SNPs as part of the Genetic Association Information Network (GAIN). We compared BPAD patients without any headache (n=699) to BPAD patients with doctor diagnosed migraine (n=56). The strongest evidence for association was found for several SNPs in a 317 kb region encompassing the uncharacterized gene KIAA0564 (e.g. rs9566845 (OR=4.98 (95%CI: 2.6–9.48), p= 7.7 ×10−8) and rs9566867 (p= 8.2 × 10−8)). Although the level of significance was significanlty reduced when using the Fisher’s Exact test (due to the low count of cases with migraine); rs9566845 p= 1.4 ×10−5 and rs9566867 p= 1.5 × 10−5, this region remained the most prominent finding. Furthermore, marker rs9566845 was genotyped and found associated with migraine in an independent Norwegian sample of adult ADHD patients with and without co-morbid migraine (n=131 and n=324 respectively), OR=2.42 (1.18–4.97), p=0.013. This is the first GWAS examining patients with bipolar disorder and co-morbid migraine. These data suggest that genetic variants in the KIAA0564 gene region may predispose to migraine headaches in subgroups of patients with both BPAD and ADHD.