Cross-disorder genomewide analysis of schizophrenia, bipolar disorder, and depression.
Cross-disorder genomewide analysis of schizophrenia, bipolar disorder, and depression.
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精神分裂症，躁郁症和抑郁症的跨disor阶层基因组分析。
DOI：
10.1176/appi.ajp.2010.09091335
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发表时间：
2010-10
期刊：
影响因子：
--
通讯作者：
Smoller JW
中科院分区：
文献类型：
--
作者：
Huang J;Perlis RH;Lee PH;Rush AJ;Fava M;Sachs GS;Lieberman J;Hamilton SP;Sullivan P;Sklar P;Purcell S;Smoller JW
家庭和双胞胎研究表明，精神病和情绪障碍的遗传影响有很大的重叠。连锁和候选基因研究也表明精神分裂症（SCZ），双相情感障碍（BPD）和重度抑郁症（MDD）之间存在重叠。本研究的目的是应用全基因组关联研究（GWAS）分析来解决遗传效应对这些疾病的特异性。我们结合了来自SCZ（CATIE，基因分型n = 741）、BPD（STEP-BD，n = 1575）和MDD（星星 *D，n= 1938）以及精神病学筛选对照（NIMH-GI对照，n = 1204）的三项大型有效性研究的GWAS数据。我们采用了两阶段的分析程序，包括一个综合测试的等位基因频率差异的情况下，对照组，然后通过模型选择步骤，以确定最佳拟合模型的等位基因效应的疾病。肾上腺髓质素（ADM）基因附近的单核苷酸多态性（rs6484218，p = 3.93 × 10−8）的结果最强，最佳拟合模型表明该效应是双相II型障碍特有的。我们还观察到的证据表明，几个基因可能具有超越临床诊断界限的作用，包括NPAS 3的变体，其在SCZ、BPD和MDD中显示出多效性作用。这项研究提供了第一个全基因组的重要证据，表明精神病理学中染色体11 p15上ADM基因附近的变异，其影响似乎是双相II型障碍所特有的。尽管我们没有检测到全基因组范围内交叉障碍影响的重要证据，但我们的研究提供了证据，表明对主要精神疾病既有多效性又有障碍特异性影响，并说明了一种剖析情绪和精神病障碍遗传基础的方法，可以为未来的大规模交叉障碍GWAS分析提供信息。
Family and twin studies indicate substantial overlap of genetic influences on psychotic and mood disorders. Linkage and candidate gene studies have also suggested overlap across schizophrenia (SCZ), bipolar disorder (BPD), and major depressive disorder (MDD). The objective of this study was to apply genomewide association study (GWAS) analysis to address the specificity of genetic effects on these disorders. We combined GWAS data from three large effectiveness studies of SCZ (CATIE, genotyped n = 741), BPD (STEP-BD, n = 1575) and MDD (STAR*D, n= 1938) and psychiatrically-screened controls (NIMH-GI controls, n = 1204). We applied a two-stage analytic procedure involving an omnibus test of allele frequency differences among case and control groups followed by a model selection step to identify the best-fitting model of allelic effects across disorders. The strongest result was seen for a single nucleotide polymorphism near the adrenomedullin (ADM) gene (rs6484218, p = 3.93 × 10−8), with the best-fitting model indicating that the effect is specific to bipolar II disorder. We also observed evidence suggesting that several genes may have effects that transcend clinical diagnostic boundaries including variants in NPAS3 that showed pleiotropic effects across SCZ, BPD, and MDD. This study provides the first genomewide significant evidence implicating variants near the ADM gene on chromosome 11p15 in psychopathology, with effects that appear to be specific to bipolar II disorder. Although we do not detect genomewide significant evidence of cross-disorder effects, our study provides evidence that there are both pleiotropic and disorder-specific effects on major mental illness and illustrates an approach to dissecting the genetic basis of mood and psychotic disorders that can inform future large-scale cross-disorder GWAS analyses.
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DOI：
10.1073/pnas.0405310101
发表时间：
2004-09-14
影响因子：
11.1
作者：
Erbel-Sieler, C;Dudley, C;McKnight, SL
通讯作者：
McKnight, SL
影响因子：
2
作者：
Bassett, AS;Chow, EWC;Gatzoulis, MA
通讯作者：
Gatzoulis, MA
DOI：
10.1073/pnas.0803174105
发表时间：
2008-08-26
影响因子：
11.1
作者：
Fernandez, Ana P.;Serrano, Julia;Martinez, Alfredo
通讯作者：
Martinez, Alfredo
影响因子：
30.8
作者：
Ferreira, Manuel A. R.;O'Donovan, Michael C.;Meng, Yan A.;Jones, Ian R.;Ruderfer, Douglas M.;Jones, Lisa;Fan, Jinbo;Kirov, George;Perlis, Roy H.;Green, Elaine K.;Smoller, Jordan W.;Grozeva, Detelina;Stone, Jennifer;Nikolov, Ivan;Chambert, Kimberly;Hamshere, Marian L.;Nimgaonkar, Vishwajit L.;Moskvina, Valentina;Thase, Michael E.;Caesar, Sian;Sachs, Gary S.;Franklin, Jennifer;Gordon-Smith, Katherine;Ardlie, Kristin G.;Gabriel, Stacey B.;Fraser, Christine;Blumenstiel, Brendan;Defelice, Matthew;Breen, Gerome;Gill, Michael;Morris, Derek W.;Elkin, Amanda;Muir, Walter J.;McGhee, Kevin A.;Williamson, Richard;MacIntyre, Donald J.;MacLean, Alan W.;Clair, David St;Robinson, Michelle;Van Beck, Margaret;Pereira, Ana C. P.;Kandaswamy, Radhika;McQuillin, Andrew;Collier, David A.;Bass, Nicholas J.;Young, Allan H.;Lawrence, Jacob;Ferrier, I. Nicol;Anjorin, Adebayo;Farmer, Anne;Curtis, David;Scolnick, Edward M.;McGuffin, Peter;Daly, Mark J.;Corvin, Aiden P.;Holmans, Peter A.;Blackwood, Douglas H.;Gurling, Hugh M.;Owen, Michael J.;Purcell, Shaun M.;Sklar, Pamela;Craddock, Nick
通讯作者：
Craddock, Nick
影响因子：
6.6
作者：
Craddock, N;O'Donovan, MC;Owen, MJ
通讯作者：
Owen, MJ