期刊
HUMAN HEREDITY
卷 68, 期 3, 页码 151-170出版社
KARGER
DOI: 10.1159/000224636
关键词
Cleft lip; Cleft palate; Linkage; Association; wFDR; IRF6; FOXE1; Genetics
资金
- NIH [R37-DE08559, R01-DE09886, R01-DE012472, R01-DE014677, R01-DE016148, P50-DE016215, R03-DE016632, KO2-DE015291, M01-RR00084]
- March of Dimes [6-FY01-616]
- Center for Inherited Disease Research ( CIDR)
- National Institutes of Health to The Johns Hopkins University [N01-HG-65403]
- NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR000084] Funding Source: NIH RePORTER
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [N01HG065403] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH [R01DE016148, R37DE008559, R00DE018085] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCH [R01DE008559, R01DE012472, K02DE015291, R01DE014667, R01DE009886, P50DE016215, R03DE016632] Funding Source: NIH RePORTER
Objectives: Non-syndromic orofacial clefts, i.e. cleft lip (CL) and cleft palate (CP), are among the most common birth defects. The goal of this study was to identify genomic regions and genes for CL with or without CP (CL/P). Methods: We performed linkage analyses of a 10 cM genome scan in 820 multiplex CL/P families (6,565 individuals). Significant linkage results were followed by association analyses of 1,476 SNPs in candidate genes and regions, utilizing a weighted false discovery rate (wFDR) approach to control for multiple testing and incorporate the genome scan results. Results: Significant (multipoint HLOD >= 3.2) or genome- wide- significant (HLOD >= 4.02) linkage results were found for regions 1q32, 2p13, 3q27-28, 9q21, 12p11, 14q21-24 and 16q24. SNPs in IRF6 (1q32) and in or near FOXE1 (9q21) reached formal genome- wide wFDR-adjusted significance. Further, results were phenotype dependent in that the IRF6 region results were most significant for families in which affected individuals have CL alone, and the FOXE1 region results were most significant in families in which some or all of the affected individuals have CL with CP. Conclusions: These results highlight the importance of careful phenotypic delineation in large samples of families for genetic analyses of complex, heterogeneous traits such as CL/P. Copyright (C) 2009 S. Karger AG, Basel
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据