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Comprehensive linkage and linkage heterogeneity analysis of 4344 sibling pairs affected with hypertension from the Family Blood Pressure Program

Abstract

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.. Peer Reviewed. http://deepblue.lib.umich.edu/bitstream/2027.42/56011/1/20202_ftp.pdf

Publication details

Download	, http://hdl.handle.net/2027.42/56011 http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=17266112&dopt=citation http://dx.doi.org/10.1002/gepi.20202
Publisher	Wiley Subscription Services, Inc., A Wiley Company
Contributors	Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan, Department of Medicine, University of Michigan, Ann Arbor, Michigan, Polymorphism Research Laboratory, Department of Psychiatry, University of California, San Diego, La Jolla, California, Polymorphism Research Laboratory, Department of Psychiatry, University of California, San Diego, La Jolla, California, Department of Genetics, University of Texas and Houston Health Science Center, Houston, Texas, Department of Genetics, University of Texas and Houston Health Science Center, Houston, Texas, Division of Biostatistics, Washington University, St. Louis, Missouri, Division of Biostatistics, Washington University, St. Louis, Missouri, Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota, Mayo Clinic College of Medicine, Rochester, Minnesota, Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, Department of Public Health Sciences and Epidemiology, John A. Burns School of Medicine, University of Hawaii and Pacific Health Research Institute, Honolulu, Hawai, Division of Biostatistics and Bioinformatics, National Health Research Institutes, Taipei, Taiwan, Polymorphism Research Laboratory, Department of Psychiatry, University of California, San Diego, La Jolla, California ; University of California, San Diego, Department of Psychiatry, 0603, 9500 Gilman Drive, La Jolla, CA 92093-0603
Repository	University of Michigan (United States)
Keywords	Life and Medical Sciences, Genetics, Biological Chemistry, Genetics, Molecular, Cellular and Developmental Biology, Health Sciences, Science