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Using an age-at-onset phenotype with interval censoring to compare methods of segregation and linkage analysis in a candidate region for elevated systolic blood pressure

BACKGROUND: Genetic studies of complex disorders such as hypertension often utilize families selected for this outcome, usually with information obtained at a single time point. Since age-at-onset for diagnosed hypertension can vary substantially between individuals, a phenotype based on long-term f...

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Autores principales: Kopciuk, Karen A, Briollais, Laurent, Demenais, Florence, Bull, Shelley B
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1866524/
https://www.ncbi.nlm.nih.gov/pubmed/14975152
http://dx.doi.org/10.1186/1471-2156-4-S1-S84
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author Kopciuk, Karen A
Briollais, Laurent
Demenais, Florence
Bull, Shelley B
author_facet Kopciuk, Karen A
Briollais, Laurent
Demenais, Florence
Bull, Shelley B
author_sort Kopciuk, Karen A
collection PubMed
description BACKGROUND: Genetic studies of complex disorders such as hypertension often utilize families selected for this outcome, usually with information obtained at a single time point. Since age-at-onset for diagnosed hypertension can vary substantially between individuals, a phenotype based on long-term follow up in unselected families can yield valuable insights into this disorder for the general population. METHODS: Genetic analyses were conducted using 2884 individuals from the largest 330 families of the Framingham Heart Study. A longitudinal phenotype was constructed using the age at an examination when systolic blood pressure (SBP) first exceeds 139 mm Hg. An interval for age-at-onset was created, since the exact time of onset was unknown. Time-fixed (sex, study cohort) and time-varying (body mass index, daily cigarette and alcohol consumption) explanatory variables were included. RESULTS: Segregation analysis for a major gene effect demonstrated that the major gene effect parameter was sensitive to the choice for age-at-onset. Linkage analyses for age-at-onset were conducted using 1537 individuals in 52 families. Evidence for putative genes identified on chromosome 17 in a previous linkage study using a quantitative SBP phenotype for these data was not confirmed. CONCLUSIONS: Interval censoring for age-at-onset should not be ignored. Further research is needed to explain the inconsistent segregation results between the different age-at-onset models (regressive threshold and proportional hazards) as well as the inconsistent linkage results between the longitudinal phenotypes (age-at-onset and quantitative).
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spelling pubmed-18665242007-05-11 Using an age-at-onset phenotype with interval censoring to compare methods of segregation and linkage analysis in a candidate region for elevated systolic blood pressure Kopciuk, Karen A Briollais, Laurent Demenais, Florence Bull, Shelley B BMC Genet Proceedings BACKGROUND: Genetic studies of complex disorders such as hypertension often utilize families selected for this outcome, usually with information obtained at a single time point. Since age-at-onset for diagnosed hypertension can vary substantially between individuals, a phenotype based on long-term follow up in unselected families can yield valuable insights into this disorder for the general population. METHODS: Genetic analyses were conducted using 2884 individuals from the largest 330 families of the Framingham Heart Study. A longitudinal phenotype was constructed using the age at an examination when systolic blood pressure (SBP) first exceeds 139 mm Hg. An interval for age-at-onset was created, since the exact time of onset was unknown. Time-fixed (sex, study cohort) and time-varying (body mass index, daily cigarette and alcohol consumption) explanatory variables were included. RESULTS: Segregation analysis for a major gene effect demonstrated that the major gene effect parameter was sensitive to the choice for age-at-onset. Linkage analyses for age-at-onset were conducted using 1537 individuals in 52 families. Evidence for putative genes identified on chromosome 17 in a previous linkage study using a quantitative SBP phenotype for these data was not confirmed. CONCLUSIONS: Interval censoring for age-at-onset should not be ignored. Further research is needed to explain the inconsistent segregation results between the different age-at-onset models (regressive threshold and proportional hazards) as well as the inconsistent linkage results between the longitudinal phenotypes (age-at-onset and quantitative). BioMed Central 2003-12-31 /pmc/articles/PMC1866524/ /pubmed/14975152 http://dx.doi.org/10.1186/1471-2156-4-S1-S84 Text en Copyright © 2003 Kopciuk et al; licensee BioMed Central Ltd http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Proceedings
Kopciuk, Karen A
Briollais, Laurent
Demenais, Florence
Bull, Shelley B
Using an age-at-onset phenotype with interval censoring to compare methods of segregation and linkage analysis in a candidate region for elevated systolic blood pressure
title Using an age-at-onset phenotype with interval censoring to compare methods of segregation and linkage analysis in a candidate region for elevated systolic blood pressure
title_full Using an age-at-onset phenotype with interval censoring to compare methods of segregation and linkage analysis in a candidate region for elevated systolic blood pressure
title_fullStr Using an age-at-onset phenotype with interval censoring to compare methods of segregation and linkage analysis in a candidate region for elevated systolic blood pressure
title_full_unstemmed Using an age-at-onset phenotype with interval censoring to compare methods of segregation and linkage analysis in a candidate region for elevated systolic blood pressure
title_short Using an age-at-onset phenotype with interval censoring to compare methods of segregation and linkage analysis in a candidate region for elevated systolic blood pressure
title_sort using an age-at-onset phenotype with interval censoring to compare methods of segregation and linkage analysis in a candidate region for elevated systolic blood pressure
topic Proceedings
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1866524/
https://www.ncbi.nlm.nih.gov/pubmed/14975152
http://dx.doi.org/10.1186/1471-2156-4-S1-S84
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