Are There Mappable Genes for Family Resemblance for the Magnitude of Intra-individual Variation in Systolic Blood Pressure? Are There Mappable Genes for Family Resemblance for the Magnitude of Intra-individual Variation in Systolic Blood Pressure?

Background: The genetic regulation of variation in intra-individual fluctuations in systolic blood pressure over time is poorly understood. Analysis of the magnitude of the average fluctuation of a person's systolic blood pressure around his or her age-adjusted trend line, however, shows moderate, albeit significant, family resemblance in Cohort 1 of the Framingham Heart Study. To determine whether genomic regions affecting this phenotype could be identified, we pursued a "model-free" multipoint quantitative linkage analysis. Results: Two different linkage methods revealed multiple nominally significant signals, two to four of which are "replicated" in Cohort 2. When both cohorts are assembled into extended pedigrees, three linkage signals remain nominally significant by one or both methods. Conclusion: Any or all of the genomic regions in the vicinity of D5S1456, D11S2359, and D20S470 may contain elements that regulate systolic blood pressure homeostasis. Background We used the rich longitudinal Framingham Heart Study data to explore the hypothesis that there is a heritable component to intra-individual variation in systolic blood pressure (SBP). Our strategy was to: 1) document family resemblance for the variability of SBP in Cohort 1; 2) use multipoint quantitative linkage analysis to identify genomic regions that may harbor genes that affect withinperson variability in SBP; and 3) replicate any findings in Cohort 2. Despite the inherent differences between the two cohorts, if one or more linkage signals are replicated, we will combine the cohorts and repeat the analysis on the extended pedigrees. We are particularly interested in assessing variation in the context of homeostatic regulation. It has been shown that a locus influencing age-adjusted SBP maps to chromosome 17q in these data [1]. We hypothesize that there is, additionally, familial resemblance for the magnitude of the fluctuations about each individual's age-related mean SBP. Since we anticipate that different individuals may have unique age-related trends (e.g., increasing SBP with age in some individuals, declining SBP in other individuals) and since we are not interested in the age-related means, per se, but rather the size of the fluctuations, we defined the phenotype as the average of absolute residual (AVGRES) obtained by regressing each person's SBP measurements on his or her age when the measurements were obtained. Because we wanted to be assured of having a from Genetic Analysis Workshop 13: Analysis of Longitudinal Family Data for Complex Diseases and Related Risk Factors New Orleans Marriott Hotel, New Orleans, LA, USA, November 11–14, 2002 Published: 31 December 2003 BMC Genetics 2003, 4(Suppl 1):S11 <supplement> <title> <p>Genetic Analysis Workshop 13: Analysis of Longitudinal Family Data for Complex Diseases and Related Risk Factors</p> </title> <editor>Laura Almasy, Christopher I Amos, Joan E Bailey-Wilson, Rita M Cantor, Cashell E Jaquish, Maria Martinez, Rosalind J Neuman, Jane M Olson, Lyle J Palmer, Stephen S Rich, M Anne Spence, Jean W MacCluer</editor> </supplement> This article is available from: http://www.biomedcentral. com/1471-2156/4/s1/S11