TY - JOUR
T1 - Genome-wide linkage analysis of longitudinal phenotypes using σ2A random effects (SSARs) fitted by Gibbs sampling
AU - Palmer, Lyle
AU - Scurrah, K.J.
AU - Tobin, M.
AU - Patel, S.R.
AU - Celedon, J.C.
AU - Burton, P.R.
AU - Weiss, S.T.
PY - 2003
Y1 - 2003
N2 - The study of change in intermediate phenotypes over time is important in genetics. In this paper we explore a new approach to phenotype definition in the genetic analysis of longitudinal phenotypes. We utilized data from the longitudinal Framingham Heart Study Family Cohort to investigate the familial aggregation and evidence for linkage to change in systolic blood pressure (SBP) over time. We used Gibbs sampling to derive sigma-squared-A-random-effects (SSARs) for the longitudinal phenotype, and then used these as a new phenotype in subsequent genome-wide linkage analyses.Additive genetic effects (sigma(A.time)(2)) were estimated to account for similar to 9.2% of the variance in the rate of change of SBP with age, while additive genetic effects (sigma(A)(2)) were estimated to account for similar to 43.9% of the variance in SBP at the mean age. The linkage results suggested that one or more major loci regulating change in SBP over time may localize to chromosomes 2, 3, 4, 6, 10, 11, 17, and 19. The results also suggested that one or more major loci regulating level of SBP may localize to chromosomes 3, 8, and 14.Our results support a genetic component to both SBP and change in SBP with age, and are consistent with a complex, multifactorial susceptibility to the development of hypertension. The use of SSARs derived from quantitative traits as input to a conventional linkage analysis appears to be valuable in the linkage analysis of genetically complex traits. We have now demonstrated in this paper the use of SSARs in the context of longitudinal family data.
AB - The study of change in intermediate phenotypes over time is important in genetics. In this paper we explore a new approach to phenotype definition in the genetic analysis of longitudinal phenotypes. We utilized data from the longitudinal Framingham Heart Study Family Cohort to investigate the familial aggregation and evidence for linkage to change in systolic blood pressure (SBP) over time. We used Gibbs sampling to derive sigma-squared-A-random-effects (SSARs) for the longitudinal phenotype, and then used these as a new phenotype in subsequent genome-wide linkage analyses.Additive genetic effects (sigma(A.time)(2)) were estimated to account for similar to 9.2% of the variance in the rate of change of SBP with age, while additive genetic effects (sigma(A)(2)) were estimated to account for similar to 43.9% of the variance in SBP at the mean age. The linkage results suggested that one or more major loci regulating change in SBP over time may localize to chromosomes 2, 3, 4, 6, 10, 11, 17, and 19. The results also suggested that one or more major loci regulating level of SBP may localize to chromosomes 3, 8, and 14.Our results support a genetic component to both SBP and change in SBP with age, and are consistent with a complex, multifactorial susceptibility to the development of hypertension. The use of SSARs derived from quantitative traits as input to a conventional linkage analysis appears to be valuable in the linkage analysis of genetically complex traits. We have now demonstrated in this paper the use of SSARs in the context of longitudinal family data.
U2 - 10.1186/1471-2156-4-S1-S12
DO - 10.1186/1471-2156-4-S1-S12
M3 - Article
C2 - 14975080
SN - 1471-2156
VL - 4, Supp. 1
SP - S12
JO - BMC Genetics
JF - BMC Genetics
IS - Suppl 1
ER -