title: A chromosome 11q quantitative-trait locus influences change of blood-pressure measurements over time in Mexican Americans of the San Antonio Family Heart Study.
abstract: Although previous genome scans have searched for quantitative-trait loci (QTLs) influencing variation in blood pressure (BP), few have investigated the rate of change in BP over time as a phenotype. Here, we compare results from genomewide scans to localize QTLs for systolic, diastolic, and mean arterial BPs (SBP, DBP, and MBP, respectively) and for rates of change in systolic, diastolic, and mean arterial BPs (rSBP, rDBP, and rMBP, respectively), with use of the longitudinal data collected about Mexican Americans of the San Antonio Family Heart Study (SAFHS). Significant evidence of linkage was found for rSBP (LOD 4.15) and for rMBP (LOD 3.94) near marker D11S4464 located on chromosome 11q24.1. This same chromosome 11q region also shows suggestive linkage to SBP (LOD 2.23) and MBP (LOD 2.37) measurements collected during the second clinic visit. Suggestive evidence of linkage to chromosome 5 was also found for rMBP, to chromosome 16 for rSBP, and to chromosomes 1, 5, 6, 7, and 21 for the single-time-point BP traits collected at the first two SAFHS clinic visits. We also present results from fine mapping the chromosome 11 QTL with use of SNP-association analysis within candidate genes identified from a bioinformatic search of the region and from whole-genome transcriptional expression data collected from 1,240 SAFHS participants. Our results show that the use of longitudinal BP data to calculate the rate of change in BP over time provides more information than do the single-time measurements, since they reveal physiological trends in the subjects that a single-time measurement could never capture. Further investigation of this region is necessary for the identification of the genetic variation responsible for QTLs influencing the rate of change in BP.
authors.affiliation: Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX 78245-0549, USA. srutherf@sfbrgenetics.org
authors.forename: Sue
authors.initials: S
authors.lastname: Rutherford
authors.forename: Guowen
authors.initials: G
authors.lastname: Cai
authors.forename: Juan C
authors.initials: JC
authors.lastname: Lopez-Alvarenga
authors.forename: Jack W
authors.initials: JW
authors.lastname: Kent
authors.forename: V Saroja
authors.initials: VS
authors.lastname: Voruganti
authors.forename: J Michael
authors.initials: JM
authors.lastname: Proffitt
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Curran
authors.forename: Mathew P
authors.initials: MP
authors.lastname: Johnson
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Dyer
authors.forename: Jeremy B
authors.initials: JB
authors.lastname: Jowett
authors.forename: Raul A
authors.initials: RA
authors.lastname: Bastarrachea
authors.forename: Larry D
authors.initials: LD
authors.lastname: Atwood
authors.forename: Harald H H
authors.initials: HH
authors.lastname: Goring
authors.forename: Jean W
authors.initials: JW
authors.lastname: Maccluer
authors.forename: Eric K
authors.initials: EK
authors.lastname: Moses
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Comuzzie
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Cole
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000235:genetics*; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D019295:Computational Biology; D005260:Female; D020869:Gene Expression Profiling; D005820:Genetic Testing; D006801:Humans; D008126:Lod Score; D008137:Longitudinal Studies; D008297:Male; D017058:Mexican Americans / Q000235:genetics*; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D013781:Texas