Comprehensive linkage and linkage heterogeneity analysis of 4344 sibling pairs affected with hypertension from the Family Blood Pressure Program.
Comprehensive linkage and linkage heterogeneity analysis of 4344 sibling pairs affected with hypertension from the Family Blood Pressure Program.
复制标题
对家庭血压计划中 4344 对患有高血压的兄弟姐妹进行综合连锁和连锁异质性分析。
DOI：
10.1002/gepi.20202
复制
发表时间：
2007
影响因子：
2.1
通讯作者：
Schork,NicholasJ
中科院分区：
文献类型：
--
作者：
Greenwood,TiffanyA;Libiger,Ondrej;Kardia,Sharon;Hanis,Craig;Morrison,AlannaC;Gu,CCharles;Rice,Treva;Miller,Michael;Turner,StephenT;Myers,RichardH;Grove,John;Hsiao,Chin-Fu;Weder,AlanB;Schork,NicholasJ
Linkage analyses of complex, multifactorial traits and diseases, such as essential hypertension, have been difficult to interpret and reconcile. Many published studies provide evidence suggesting that different genes and genomic regions influence hypertension, but knowing which of these studies reflect true positive results is challenging. The reasons for this include the diversity of analytical methods used across these studies, the different samples and sample sizes in each study, and the complicated biological underpinnings of hypertension. We have undertaken a comprehensive linkage analysis of 371 autosomal microsatellite markers genotyped on 4,334 sibling pairs affected with hypertension from five ethnic groups sampled from 13 different field centers associated with the Family Blood Pressure Program (FBPP). We used a single analytical technique known to be robust to interpretive problems associated with a lack of completely informative markers to assess evidence for linkage to hypertension both within and across the ethnic groups and field centers. We find evidence for linkage to a number of genomic regions, with the most compelling evidence from analyses that combine data across field center and ethnic groups (e.g., chromosomes 2 and 9). We also pursued linkage analyses that accommodate locus heterogeneity, which is known to plague the identification of disease susceptibility loci in linkage studies of complex diseases. We find evidence for linkage heterogeneity on chromosomes 2 and 17. Ultimately our results suggest that evidence for linkage heterogeneity can only be detected with large sample sizes, such as the FBPP, which is consistent with theoretical sample size calculations.Genet. Epidemiol. 2007. © 2007 Wiley‐Liss, Inc.
