A genome-wide association study of anorexia nervosa.
A genome-wide association study of anorexia nervosa.
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DOI：
10.1038/mp.2013.187
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发表时间：
2014-10
影响因子：
11
通讯作者：
Bulik, C. M.
中科院分区：
文献类型：
--
作者：
Boraska, V.;Franklin, C. S.;Floyd, J. A. B.;Thornton, L. M.;Huckins, L. M.;Southam, L.;Rayner, N. W.;Tachmazidou, I.;Klump, K. L.;Treasure, J.;Lewis, C. M.;Schmidt, U.;Tozzi, F.;Kiezebrink, K.;Hebebrand, J.;Gorwood, P.;Adan, R. A. H.;Kas, M. J. H.;Favaro, A.;Santonastaso, P.;Fernandez-Aranda, F.;Gratacos, M.;Rybakowski, F.;Dmitrzak-Weglarz, M.;Kaprio, J.;Keski-Rahkonen, A.;Raevuori, A.;Van Furth, E. F.;'t Landt, M. C. T. Slof-Op;Hudson, J. I.;Reichborn-Kjennerud, T.;Knudsen, G. P. S.;Monteleone, P.;Kaplan, A. S.;Karwautz, A.;Hakonarson, H.;Berrettini, W. H.;Guo, Y.;Li, D.;Schork, N. J.;Komaki, G.;Ando, T.;Inoko, H.;Esko, T.;Fischer, K.;Maennik, K.;Metspalu, A.;Baker, J. H.;Cone, R. D.;Dackor, J.;DeSocio, J. E.;Hilliard, C. E.;O'Toole, J. K.;Pantel, J.;Szatkiewicz, J. P.;Taico, C.;Zerwas, S.;Trace, S. E.;Davis, O. S. P.;Helder, S.;Buehren, K.;Burghardt, R.;de Zwaan, M.;Egberts, K.;Ehrlich, S.;Herpertz-Dahlmann, B.;Herzog, W.;Imgart, H.;Scherag, A.;Scherag, S.;Zipfel, S.;Boni, C.;Ramoz, N.;Versini, A.;Brandys, M. K.;Danner, U. N.;de Kovel, C.;Hendriks, J.;Koeleman, B. P. C.;Ophoff, R. A.;Strengman, E.;van Elburg, A. A.;Bruson, A.;Clementi, M.;Degortes, D.;Forzan, M.;Tenconi, E.;Docampo, E.;Escaramis, G.;Jimenez-Murcia, S.;Lissowska, J.;Rajewski, A.;Szeszenia-Dabrowska, N.;Slopien, A.;Hauser, J.;Karhunen, L.;Meulenbelt, I.;Slagboom, P. E.;Tortorella, A.;Maj, M.;Dedoussis, G.;Dikeos, D.;Gonidakis, F.;Tziouvas, K.;Tsitsika, A.;Papezova, H.;Slachtova, L.;Martaskova, D.;Kennedy, J. L.;Levitan, R. D.;Yilmaz, Z.;Huemer, J.;Koubek, D.;Merl, E.;Wagner, G.;Lichtenstein, P.;Breen, G.;Cohen-Woods, S.;Farmer, A.;McGuffin, P.;Cichon, S.;Giegling, I.;Herms, S.;Rujescu, D.;Schreiber, S.;Wichmann, H-E;Dina, C.;Sladek, R.;Gambaro, G.;Soranzo, N.;Julia, A.;Marsal, S.;Rabionet, R.;Gaborieau, V.;Dick, D. M.;Palotie, A.;Ripatti, S.;Widen, E.;Andreassen, O. A.;Espeseth, T.;Lundervold, A.;Reinvang, I.;Steen, V. M.;Le Hellard, S.;Mattingsdal, M.;Ntalla, I.;Bencko, V.;Foretova, L.;Janout, V.;Navratilova, M.;Gallinger, S.;Pinto, D.;Scherer, S. W.;Aschauer, H.;Carlberg, L.;Schosser, A.;Alfredsson, L.;Ding, B.;Klareskog, L.;Padyukov, L.;Courtet, P.;Guillaume, S.;Jaussent, I.;Finan, C.;Kalsi, G.;Roberts, M.;Logan, D. W.;Peltonen, L.;Ritchie, G. R. S.;Barrett, J. C.;Estivill, X.;Hinney, A.;Sullivan, P. F.;Collier, D. A.;Zeggini, E.;Bulik, C. M.
神经性厌食症 (AN) 是一种复杂的遗传性饮食失调症，其特征是危险的低体重。候选基因研究和最初的全基因组关联研究（GWAS）都没有产生显着且可重复的结果。作为 AN 遗传联盟 (GCAN) 和 Wellcome Trust 病例对照联盟 3 (WTCCC3) 的一部分，我们对来自 14 个国家（15 个地点）的 2,907 例 AN 病例和 14,860 个祖先匹配对照进行了 GWAS。在每个层中进行个体关联分析，并对所有 15 个发现数据集进行荟萃分析。在 2,677 个独立 AN 病例和 8,629 个欧洲血统对照以及来自日本的 458 个 AN 病例和 421 个对照中，对 76 个（72 个独立）SNP 进行了计算机模拟（2 个数据集）或从头（13 个数据集）复制基因分型。最终的发现和复制数据集的全球荟萃分析包括 5,551 个 AN 病例和 21,080 个对照。进行了 AN 亚型分析（1,606 例 AN 限制；1,445 例 AN 暴食清除）。没有发现达到全基因组意义。两个内含子变体暗示相关：SOX2OT 中的 rs9839776 (P=3.01×10-7) 和 PPP3CA 中的 rs17030795 (P=5.84×10-6)。另外两个信号是欧洲人特有的：CUL3 和 FAM124B 之间的 rs1523921 (P=5.76×10-6) 和 SPATA13 附近的 rs1886797 (P=8.05×10-6)。将发现结果与复制结果进行比较，76% 的效应处于同一方向，这一观察结果极不可能是偶然的 (P=4×10-6)，强烈表明真实的发现存在，但我们的样本（迄今为止报告的最大样本）不足以进行检测。大量基因分型 AN 病例对照样本的积累应该是该领域的当务之急。
Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2,907 cases with AN from 14 countries (15 sites) and 14,860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery datasets. Seventy-six (72 independent) SNPs were taken forward for in silico (two datasets) or de novo (13 datasets) replication genotyping in 2,677 independent AN cases and 8,629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication datasets comprised 5,551 AN cases and 21,080 controls. AN subtype analyses (1,606 AN restricting; 1,445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01×10-7) in SOX2OT and rs17030795 (P=5.84×10-6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76×10-6) between CUL3 and FAM124B and rs1886797 (P=8.05×10-6) near SPATA13. Comparing discovery to replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4×10-6), strongly suggesting that true findings exist but that our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.
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影响因子：
3.5
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通讯作者：
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通讯作者：
Grant, Struan F. A.
DOI：
10.1002/ajmg.b.32087
发表时间：
2012-10
影响因子：
2.8
作者：
Boraska, Vesna;Davis, Oliver S. P.;Cherkas, Lynn F.;Helder, Sietske G.;Harris, Juliette;Krug, Isabel;Pei-Chi Liao, Thomas;Treasure, Janet;Ntalla, Ioanna;Karhunen, Leila;Keski-Rahkonen, Anna;Christakopoulou, Danai;Raevuori, Anu;Shin, So-Youn;Dedoussis, George V.;Kaprio, Jaakko;Soranzo, Nicole;Spector, Tim D.;Collier, David A.;Zeggini, Eleftheria
通讯作者：
Zeggini, Eleftheria