Confirming genes influencing risk to cleft lip with/without cleft palate in a case-parent trio study.
Confirming genes influencing risk to cleft lip with/without cleft palate in a case-parent trio study.
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DOI：
10.1007/s00439-013-1283-6
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发表时间：
2013-07
期刊：
影响因子：
5.3
通讯作者：
Ruczinski, I.
中科院分区：
文献类型：
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作者：
Beaty, T. H.;Taub, M. A.;Scott, A. F.;Murray, J. C.;Marazita, M. L.;Schwender, H.;Parker, M. M.;Hetmanski, J. B.;Balakrishnan, P.;Mansilla, M. A.;Mangold, E.;Ludwig, K. U.;Noethen, M. M.;Rubini, M.;Elcioglu, N.;Ruczinski, I.
通过一个孤立的，非综合征性唇腭裂或腭裂（CL/P）确定的1,108例病例-父母三人组的集合被用来复制全基因组关联研究（GWAS）的结果，其中四个不同的基因/区域被确定为影响CL/P的风险。最初被鉴定为显示全基因组意义的所有四个基因（IRF 6，ABCA 4和MAF，加上8 q24区域）在这个独立的三人组样本（主要是欧洲和东南亚血统）中得到了证实。此外，在原始研究中被归类为“第二层”命中的8个基因（PAX 7，THADA，COL 8A 1/FILIP 1 L，DCAF 4L 2，GADD 45 G，NTN 1，RBFOX 3和FOXE 1）在该复制样本中显示出连锁和关联的证据。原始GWAS trios和这些复制trios之间的荟萃分析显示PAX 7，COL 8A 1/FILIP 1 L和NTN 1实现了全基因组意义。对这33个基因与母亲吸烟之间的基因-环境相互作用的测试发现了与另外两个基因相互作用的证据：欧洲母亲中的GRID 2和ELAVL 2（吸烟率高于亚洲母亲）。基因-基因相互作用（上位性）的正式测试未能以任何简单的方式显示统计学相互作用的证据。这项研究证实了许多不同的基因影响CL/P的风险。
A collection of 1,108 case-parent trios ascertained through an isolated, non-syndromic cleft lip with or without cleft palate (CL/P) was used to replicate the findings from a genome-wide association study (GWAS) conducted by where four different genes/regions were identified as influencing risk to CL/P. Tagging SNPs for 33 different genes were genotyped (1,269 SNPs). All four of the genes originally identified as showing genome-wide significance (IRF6, ABCA4 and MAF, plus the 8q24 region) were confirmed in this independent sample of trios (who were primarily of European and Southeast Asian ancestry). In addition, eight genes classified as ‘second tier’ hits in the original study (PAX7, THADA, COL8A1/FILIP1L, DCAF4L2, GADD45G, NTN1, RBFOX3 and FOXE1) showed evidence of linkage and association in this replication sample. Meta-analysis between the original GWAS trios and these replication trios showed PAX7, COL8A1/FILIP1L and NTN1 achieved genome-wide significance. Tests for gene-environment interaction between these 33 genes and maternal smoking found evidence for interaction with two additional genes: GRID2 and ELAVL2 among European mothers (who had a higher rate of smoking than Asian mothers). Formal tests for gene-gene interaction (epistasis) failed to show evidence of statistical interaction in any simple fashion. This study confirms that many different genes influence risk to CL/P.
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DOI：
10.1038/nrg2579
发表时间：
2009-06
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
Cordell HJ
通讯作者：
Cordell HJ
影响因子：
30.8
作者：
Birnbaum, Stefanie;Ludwig, Kerstin U.;Mangold, Elisabeth
通讯作者：
Mangold, Elisabeth
影响因子：
1.8
作者：
Marazita ML;Lidral AC;Murray JC;Field LL;Maher BS;Goldstein McHenry T;Cooper ME;Govil M;Daack-Hirsch S;Riley B;Jugessur A;Felix T;Morene L;Mansilla MA;Vieira AR;Doheny K;Pugh E;Valencia-Ramirez C;Arcos-Burgos M
通讯作者：
Arcos-Burgos M
DOI：
10.1093/bioinformatics/btq340
发表时间：
2010-09-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Willer CJ;Li Y;Abecasis GR
通讯作者：
Abecasis GR
影响因子：
30.8
作者：
通讯作者：
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