Identification of TNFSF13, SPATC1L, SLC22A25 and SALL4 as novel susceptibility loci for atrial fibrillation by an exome‑wide association study.
Identification of TNFSF13, SPATC1L, SLC22A25 and SALL4 as novel susceptibility loci for atrial fibrillation by an exome‑wide association study.
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DOI：
10.3892/mmr.2017.7334
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发表时间：
2017-11
影响因子：
3.4
通讯作者：
Tanaka M
中科院分区：
文献类型：
--
作者：
Yamada Y;Sakuma J;Takeuchi I;Yasukochi Y;Kato K;Oguri M;Fujimaki T;Horibe H;Muramatsu M;Sawabe M;Fujiwara Y;Taniguchi Y;Obuchi S;Kawai H;Shinkai S;Mori S;Arai T;Tanaka M
进行了一项外显子组关联研究（EWAS），以确定遗传变异，特别是低频或罕见的编码变异，具有中等至大的效应量，使日本人对房颤易感。使用Illumina HumanExome-12 DNA Analysis BeadChip或Infinium Exome-24 BeadChip阵列对13，166名受试者（884名房颤患者和12，282名对照）进行了房颤的EWAS。使用Fisher精确检验检查了房颤与通过质量控制的41，243个单核苷酸多态性（SNP）的等位基因频率的相关性。根据Bonferroni校正，P<1.21×10−6被认为具有统计学显著性。房颤的EWAS显示，122个SNP与这种情况显著相关。通过调整年龄、性别和高血压患病率的多变量logistic回归分析，进一步检查所确定的SNP与房颤的关联。8个SNPs相关（P<0.01），其中TNF超家族成员13的rs 11552708 [G/A（G67 R）]（TNFSF 13;显性模型; P=9.36×10−9;比值比，0.58），精子发生和中心粒相关的rs 113710653 [C/T（E231 K）] 1样（SPATC 1 L;显性模型; P=1.09×10−5;比值比，3.27）和溶质携带者家族22成员25的rs 11231397 [G/C（R300 T）]（SLC 22 A25;加性模型; P=3.71×10−5;比值比，1.77）与这种情况显著相关（P<1.02×10−4）。rs 113710653的次要T等位基因和rs 11231397的次要C等位基因是房颤的危险因素，而rs 11552708的次要A等位基因对这种情况具有保护作用。此外，SALL 4的rs77538589 [C/T（G117 R）]表现出与房颤相关的趋势（显性模型; P=0.0002;比值比，1.88），次要T等位基因代表该疾病的风险因素。因此，TNFSF 13、SPATC 1 L、SLC 22 A25和SALL 4可能是日本人群中房颤的新易感基因座。
An exome-wide association study (EWAS) was performed to identify genetic variants, particularly low-frequency or rare coding variants with a moderate to large effect size, that confer susceptibility to atrial fibrillation in Japanese. The EWAS for atrial fibrillation was performed with 13,166 subjects (884 patients with atrial fibrillation and 12,282 controls) using an Illumina HumanExome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays. The association of atrial fibrillation with allele frequencies of 41,243 single nucleotide polymorphisms (SNPs) that passed quality control was examined with Fisher's exact test. Based on Bonferroni's correction, a P<1.21×10−6 was considered statistically significant. The EWAS for atrial fibrillation revealed that 122 SNPs were significantly associated with this condition. The association of the identified SNPs to atrial fibrillation was further examined by multivariable logistic regression analysis with adjustment for age, sex and the prevalence of hypertension. Eight SNPs were related (P<0.01) to atrial fibrillation, among which three polymorphisms, rs11552708 [G/A (G67R)]of TNF superfamily member 13 (TNFSF13; dominant model; P=9.36×10−9; odds ratio, 0.58), rs113710653 [C/T (E231 K)] of spermatogenesis and centriole associated 1 like (SPATC1L; dominant model; P=1.09×10−5; odds ratio, 3.27), and rs11231397 [G/C (R300T)] of solute carrier family 22 member 25 (SLC22A25; additive model; P=3.71×10−5; odds ratio, 1.77), were significantly (P<1.02×10−4) associated with this condition. The minor T allele of rs113710653 and the minor C allele of rs11231397 were risk factors for atrial fibrillation, whereas the minor A allele of rs11552708 was protective against this condition. In addition, rs77538589 [C/T (G117R)] of SALL4 exhibited a tendency to be associated with atrial fibrillation (dominant model; P=0.0002; odds ratio, 1.88), with the minor T allele representing a risk factor for this condition. TNFSF13, SPATC1L, SLC22A25 and SALL4 may thus be novel susceptibility loci for atrial fibrillation in the Japanese population.
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影响因子：
30.8
作者：
Ellinor, Patrick T.;Lunetta, Kathryn L.;Glazer, Nicole L.;Pfeufer, Arne;Alonso, Alvaro;Chung, Mina K.;Sinner, Moritz F.;de Bakker, Paul I. W.;Mueller, Martina;Lubitz, Steven A.;Fox, Ervin;Darbar, Dawood;Smith, Nicholas L.;Smith, Jonathan D.;Schnabel, Renate B.;Soliman, Elsayed Z.;Rice, Kenneth M.;Van Wagoner, David R.;Beckmann, Britt-M;van Noord, Charlotte;Wang, Ke;Ehret, Georg B.;Rotter, Jerome I.;Hazen, Stanley L.;Steinbeck, Gerhard;Smith, Albert V.;Launer, Lenore J.;Harris, Tamara B.;Makino, Seiko;Nelis, Mari;Milan, David J.;Perz, Siegfried;Esko, Tonu;Koettgen, Anna;Moebus, Susanne;Newton-Cheh, Christopher;Li, Man;Moehlenkamp, Stefan;Wang, Thomas J.;Kao, W. H. Linda;Vasan, Ramachandran S.;Noethen, Markus M.;MacRae, Calum A.;Stricker, Bruno H. Ch;Hofman, Albert;Uitterlinden, Andre G.;Levy, Daniel;Boerwinkle, Eric;Metspalu, Andres;Topol, Eric J.;Chakravarti, Aravinda;Gudnason, Vilmundur;Psaty, Bruce M.;Roden, Dan M.;Meitinger, Thomas;Wichmann, H-Erich;Witteman, Jacqueline C. M.;Barnard, John;Arking, Dan E.;Benjamin, Emelia J.;Heckbert, Susan R.;Kaeaeb, Stefan
通讯作者：
Kaeaeb, Stefan
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影响因子：
30.8
作者：
Kiryluk, Krzysztof;Li, Yifu;Scolari, Francesco;Sanna-Cherchi, Simone;Choi, Murim;Verbitsky, Miguel;Fasel, David;Lata, Sneh;Prakash, Sindhuri;Shapiro, Samantha;Fischman, Clara;Snyder, Holly J.;Appel, Gerald;Izzi, Claudia;Viola, Battista Fabio;Dallera, Nadia;Del Vecchio, Lucia;Barlassina, Cristina;Salvi, Erika;Bertinetto, Francesca Eleonora;Amoroso, Antonio;Savoldi, Silvana;Rocchietti, Marcella;Amore, Alessandro;Peruzzi, Licia;Coppo, Rosanna;Salvadori, Maurizio;Ravani, Pietro;Magistroni, Riccardo;Ghiggeri, Gian Marco;Caridi, Gianluca;Bodria, Monica;Lugani, Francesca;Allegri, Landino;Delsante, Marco;Maiorana, Mariarosa;Magnano, Andrea;Frasca, Giovanni;Boer, Emanuela;Boscutti, Giuliano;Ponticelli, Claudio;Mignani, Renzo;Marcantoni, Carmelita;Di Landro, Domenico;Santoro, Domenico;Pani, Antonello;Polci, Rosaria;Feriozzi, Sandro;Chicca, Silvana;Galliani, Marco;Gigante, Maddalena;Gesualdo, Loreto;Zamboli, Pasquale;Battaglia, Giovanni Giorgio;Garozzo, Maurizio;Maixnerova, Dita;Tesar, Vladimir;Eitner, Frank;Rauen, Thomas;Floege, Juergen;Kovacs, Tibor;Nagy, Judit;Mucha, Krzysztof;Paczek, Leszek;Zaniew, Marcin;Mizerska-Wasiak, Malgorzata;Roszkowska-Blaim, Maria;Pawlaczyk, Krzysztof;Gale, Daniel;Barratt, Jonathan;Thibaudin, Lise;Berthoux, Francois;Canaud, Guillaume;Boland, Anne;Metzger, Marie;Panzer, Ulf;Suzuki, Hitoshi;Goto, Shin;Narita, Ichiei;Caliskan, Yasar;Xie, Jingyuan;Hou, Ping;Chen, Nan;Zhang, Hong;Wyatt, Robert J.;Novak, Jan;Julian, Bruce A.;Feehally, John;Stengel, Benedicte;Cusi, Daniele;Lifton, Richard P.;Gharavi, Ali G.
通讯作者：
Gharavi, Ali G.
影响因子：
9.1
作者：
Jonsson, MV;Szodoray, P;Skarstein, K
通讯作者：
Skarstein, K
影响因子：
4.4
作者：
Jacobsson, Josefin A.;Haitina, Tatjana;Fredriksson, Robert
通讯作者：
Fredriksson, Robert
动脉粥样硬化的炎症。
DOI：
10.1161/atvbaha.108.179705
发表时间：
2012-09
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
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作者：
Libby P
通讯作者：
Libby P