Selectivity in genetic association with sub-classified migraine in women.
Selectivity in genetic association with sub-classified migraine in women.
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在妇女中与亚分类的偏头痛的遗传关联中的选择性。
DOI：
10.1371/journal.pgen.1004366
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发表时间：
2014-05
期刊：
影响因子：
4.5
通讯作者：
International Headache Genetics Consortium
中科院分区：
文献类型：
--
作者：
Chasman DI;Anttila V;Buring JE;Ridker PM;Schürks M;Kurth T;International Headache Genetics Consortium
偏头痛不仅可以根据偏头痛先兆（MA）的存在或偏头痛先兆（MO）的不存在进行细分，还可以根据伴随偏头痛发作的其他特征进行细分，例如头痛恐惧症、声音恐惧症、恶心等，所有这些都被头痛疾病国际分类正式认可。目前尚不清楚先兆状态和其他偏头痛特征如何与潜在的偏头痛病理生理学相关。最近的全基因组关联研究（GWAS）已经确定了12个独立的基因座，其中单核苷酸多态性（SNP）与偏头痛相关。使用似然框架，我们探索了这些SNP与偏头痛的选择性关联，根据先兆状态和一个大型人群为基础的女性队列中的其他特征进行细分，包括3，003名活动性偏头痛患者和18，108名无偏头痛患者。五个位点与偏头痛的关联达到严格的显著性，其中四个对偏头痛的亚分类具有选择性，包括MO的rs11172113（LRP 1）。与偏头痛相关的基因座数量增加到11个提示意义阈值，包括5个额外的选择性关联MO，但没有MA。没有两个SNPs显示出与偏头痛特征选择性相关的相似模式。在一个极端，SNPs rs6790925（靠近TGFBR 2）和rs2274316（MEF2D）与偏头痛总体、MA或MO无关，但对偏头痛有选择性，偏头痛通过一个或多个额外的偏头痛特征的存在而细分。相比之下，SNP rs7577262（TRPM8）与偏头痛总体相关，并且对任何偏头痛特征显示很少或没有选择性。研究结果强调了偏头痛病理生理学的多价性，并表明根据先兆状态和用于偏头痛临床表征的其他诊断特征对偏头痛进行分层的分析可能有利于对偏头痛遗传影响的全面了解。偏头痛是最常见的和使人衰弱的神经系统疾病之一。偏头痛的诊断标准识别多种症状，包括存在或不存在先兆的主要二分分类，通常是视觉障碍现象，以及其他如对光或声音敏感，恶心，我们探讨了最近发现的12种与常见偏头痛相关的遗传变异中是否有任何一种可能与偏头痛亚临床症状有选择性相关。根据先兆状态或9个额外的偏头痛特征分类，中年女性人群包括3，003名偏头痛患者和18，180名非偏头痛患者。12个遗传变异中有5个符合与偏头痛相关的最严格的显著性标准，其中4个与亚分类的偏头痛有选择性相关，包括一个对无先兆的偏头痛有选择性。在提示意义上，所有剩余的遗传变异对偏头痛的亚类都是选择性的，尽管没有两个变异显示出相同的选择性模式。选择性模式表明非常不同的贡献偏头痛的病理生理学之间的12个位点和它们的牵连基因。此外，研究结果表明，未来发现新的偏头痛易感基因座的努力将受益于考虑与亚分类偏头痛朝着更具体的诊断和个性化治疗的最终目标的关联。
Migraine can be sub-classified not only according to presence of migraine aura (MA) or absence of migraine aura (MO), but also by additional features accompanying migraine attacks, e.g. photophobia, phonophobia, nausea, etc. all of which are formally recognized by the International Classification of Headache Disorders. It remains unclear how aura status and the other migraine features may be related to underlying migraine pathophysiology. Recent genome-wide association studies (GWAS) have identified 12 independent loci at which single nucleotide polymorphisms (SNPs) are associated with migraine. Using a likelihood framework, we explored the selective association of these SNPs with migraine, sub-classified according to aura status and the other features in a large population-based cohort of women including 3,003 active migraineurs and 18,108 free of migraine. Five loci met stringent significance for association with migraine, among which four were selective for sub-classified migraine, including rs11172113 (LRP1) for MO. The number of loci associated with migraine increased to 11 at suggestive significance thresholds, including five additional selective associations for MO but none for MA. No two SNPs showed similar patterns of selective association with migraine characteristics. At one extreme, SNPs rs6790925 (near TGFBR2) and rs2274316 (MEF2D) were not associated with migraine overall, MA, or MO but were selective for migraine sub-classified by the presence of one or more of the additional migraine features. In contrast, SNP rs7577262 (TRPM8) was associated with migraine overall and showed little or no selectivity for any of the migraine characteristics. The results emphasize the multivalent nature of migraine pathophysiology and suggest that a complete understanding of the genetic influence on migraine may benefit from analyses that stratify migraine according to both aura status and the additional diagnostic features used for clinical characterization of migraine. Migraine is among the most common and debilitating neurological disorders. Diagnostic criteria for migraine recognize a variety of symptoms including a primary dichotomous classification for the presence or absence of aura, typically a visual disturbance phenomenon, as well as others such as sensitivity to light or sound, and nausea, etc. We explored whether any of 12 recently discovered genetic variants associated with common migraine might have selective association for migraine sub-classified by aura status or nine additional migraine features in a population of middle-aged women including 3,003 migraineurs and 18,180 non-migraineurs. Five of the 12 genetic variants met the most stringent significance criterion for association with migraine, among which four had selective association with sub-classified migraine, including one that was selective for migraine without aura. At suggestive significance, all of the remaining genetic variants were selective for sub-classifications of migraine although no two variants showed the same pattern of selectivity. The selectivity patterns suggest very different contributions to migraine pathophysiology among the 12 loci and their implicated genes. Further, the results suggest that future discovery efforts for new migraine susceptibility loci would benefit by considering associations with sub-classified migraine toward the ultimate goals of more specific diagnosis and personalized treatment.
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影响因子：
120.7
作者：
Kurth, Tobias;Gaziano, J. Michael;Buring, Julie E.
通讯作者：
Buring, Julie E.
影响因子：
9.8
作者：
Bown, Matthew J.;Jones, Gregory T.;Samani, Nilesh J.
通讯作者：
Samani, Nilesh J.
影响因子：
30.8
作者：
Lee, S. Hong;Ripke, Stephan;Neale, Benjamin M.;Faraone, Stephen V.;Purcell, Shaun M.;Perlis, Roy H.;Mowry, Bryan J.;Thapar, Anita;Goddard, Michael E.;Witte, John S.;Absher, Devin;Agartz, Ingrid;Akil, Huda;Amin, Farooq;Andreassen, Ole A.;Anjorin, Adebayo;Anney, Richard;Anttila, Verneri;Arking, Dan E.;Asherson, Philip;Azevedo, Maria H.;Backlund, Lena;Badner, Judith A.;Bailey, Anthony J.;Banaschewski, Tobias;Barchas, Jack D.;Barnes, Michael R.;Barrett, Thomas B.;Bass, Nicholas;Battaglia, Agatino;Bauer, Michael;Bayes, Monica;Bellivier, Frank;Bergen, Sarah E.;Berrettini, Wade;Betancur, Catalina;Bettecken, Thomas;Biederman, Joseph;Binder, Elisabeth B.;Black, Donald W.;Blackwood, Douglas H. R.;Bloss, Cinnamon S.;Boehnke, Michael;Boomsma, Dorret I.;Breen, Gerome;Breuer, Rene;Bruggeman, Richard;Cormican, Paul;Buccola, Nancy G.;Buitelaar, Jan K.;Bunney, William E.;Buxbaum, Joseph D.;Byerley, William F.;Byrne, Enda M.;Caesar, Sian;Cahn, Wiepke;Cantor, Rita M.;Casas, Miguel;Chakravarti, Aravinda;Chambert, Kimberly;Choudhury, Khalid;Cichon, Sven;Cloninger, C. Robert;Collier, David A.;Cook, Edwin H.;Coon, Hilary;Cormand, Bru;Corvin, Aiden;Coryell, William H.;Craig, David W.;Craig, Ian W.;Crosbie, Jennifer;Cuccaro, Michael L.;Curtis, David;Czamara, Darina;Datta, Susmita;Dawson, Geraldine;Day, Richard;De Geus, Eco J.;Degenhardt, Franziska;Djurovic, Srdjan;Donohoe, Gary J.;Doyle, Alysa E.;Duan, Jubao;Dudbridge, Frank;Duketis, Eftichia;Ebstein, Richard P.;Edenberg, Howard J.;Elia, Josephine;Ennis, Sean;Etain, Bruno;Fanous, Ayman;Farmer, Anne E.;Ferrier, I. 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E.;Mahon, Pamela B.;Maier, Wolfgang;Malhotra, Anil K.;Mane, Shrikant M.;Martin, Christa L.;Martin, Nicholas G.;Mattheisen, Manuel;Matthews, Keith;Mattingsdal, Morten;McCarroll, Steven A.;McGhee, Kevin A.;McGough, James J.;McGrath, Patrick J.;McGuffin, Peter;McInnis, Melvin G.;McIntosh, Andrew;McKinney, Rebecca;McLean, Alan W.;McMahon, Francis J.;McMahon, William M.;McQuillin, Andrew;Medeiros, Helena;Medland, Sarah E.;Meier, Sandra;Melle, Ingrid;Meng, Fan;Meyer, Jobst;Middeldorp, Christel M.;Middleton, Lefkos;Milanova, Vihra;Miranda, Ana;Monaco, Anthony P.;Montgomery, Grant W.;Moran, Jennifer L.;Moreno-De-Luca, Daniel;Morken, Gunnar;Morris, Derek W.;Morrow, Eric M.;Moskvina, Valentina;Muglia, Pierandrea;Muehleisen, Thomas W.;Muir, Walter J.;Mueller-Myhsok, Bertram;Murtha, Michael;Myers, Richard M.;Myin-Germeys, Inez;Neale, Michael C.;Nelson, Stan F.;Nievergelt, Caroline M.;Nikolov, Ivan;Nimgaonkar, Vishwajit;Nolen, Willem A.;Noethen, Markus M.;Nurnberger, John I.;Nwulia, Evaristus A.;Nyholt, Dale R.;O'Dushlaine, Colm;Oades, Robert D.;Olincy, Ann;Oliveira, Guiomar;Olsen, Line;Ophoff, Roel A.;Osby, Urban;Owen, Michael J.;Palotie, Aarno;Parr, Jeremy R.;Paterson, Andrew D.;Pato, Carlos N.;Pato, Michele T.;Penninx, Brenda W.;Pergadia, Michele L.;Pericak-Vance, Margaret A.;Pickard, Benjamin S.;Pimm, Jonathan;Piven, Joseph;Posthuma, Danielle;Potash, James B.;Poustka, Fritz;Propping, Peter;Puri, Vinay;Quested, Digby J.;Quinn, Emma M.;Antoni Ramos-Quiroga, Josep;Rasmussen, Henrik B.;Raychaudhuri, Soumya;Rehnstroem, Karola;Reif, Andreas;Ribases, Marta;Rice, John P.;Rietschel, Marcella;Roeder, Kathryn;Roeyers, Herbert;Rossin, Lizzy;Rothenberger, Aribert;Rouleau, Guy;Ruderfer, Douglas;Rujescu, Dan;Sanders, Alan R.;Sanders, Stephan J.;Santangelo, Susan L.;Sergeant, Joseph A.;Schachar, Russell;Schalling, Martin;Schatzberg, Alan F.;Scheftner, William A.;Schellenberg, Gerard D.;Scherer, Stephen W.;Schork, Nicholas J.;Schulze, Thomas G.;Schumacher, Johannes;Schwarz, Markus;Scolnick, Edward;Scott, Laura J.;Shi, Jianxin;Shilling, Paul D.;Shyn, Stanley I.;Silverman, Jeremy M.;Slager, Susan L.;Smalley, Susan L.;Smit, Johannes H.;Smith, Erin N.;Sonuga-Barke, Edmund J. 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通讯作者：
Wray, Naomi R.
影响因子：
2.1
作者：
Li, Yun;Willer, Cristen J.;Ding, Jun;Scheet, Paul;Abecasis, Goncalo R.
通讯作者：
Abecasis, Goncalo R.
影响因子：
30.8
作者：
通讯作者：
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