Use of tree-based models to identify subgroups and increase power to detect linkage to cardiovascular disease traits

BackgroundOur goal was to identify subgroups of sib pairs from the Framingham Heart Study data set that provided higher evidence of linkage to particular candidate regions for cardiovascular disease traits. The focus of this method is not to claim identification of significant linkage to a particular locus but to show that tree models can be used to identify subgroups for use in selected sib-pair sampling schemes.ResultsWe report results using a novel recursive partitioning procedure to identify subgroups of sib pairs with increased evidence of linkage to systolic blood pressure and other cardiovascular disease-related quantitative traits, using the Framingham Heart Study data set provided by the Genetic Analysis Workshop 13. This procedure uses a splitting rule based on Haseman-Elston regression that recursively partitions sib-pair data into homogeneous subgroups.ConclusionsUsing this procedure, we identified a subgroup definition for use as a selected sib-pair sampling scheme. Using the characteristics that define the subgroup with higher evidence for linkage, we have identified an area of focus for further study.

[1]  J. Norris,et al.  Genome scan linkage results for longitudinal systolic blood pressure phenotypes in subjects from the Framingham Heart Study , 2003, BMC Genetics.

[2]  Leo Breiman,et al.  Classification and Regression Trees , 1984 .

[3]  M. Province,et al.  19 Classification methods for confronting heterogeneity , 2001 .

[4]  R H Myers,et al.  Evidence for a gene influencing the TG/HDL-C ratio on chromosome 7q32.3-qter: a genome-wide scan in the Framingham study. , 2000, Human molecular genetics.

[5]  L. Farrer,et al.  Evidence for linkage between essential hypertension and a putative locus on human chromosome 17. , 1999, Hypertension.

[6]  T. Niu,et al.  An extreme-sib-pair genome scan for genes regulating blood pressure. , 1999, American journal of human genetics.

[7]  A. Tonkin,et al.  Genome-Wide Linkage Analysis of the Acute Coronary Syndrome Suggests a Locus on Chromosome 2 , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[8]  S. Douma,et al.  Angiotensin converting enzyme gene polymorphism is not related to essential hypertension in a Greek population. , 1995, American journal of hypertension.

[9]  M A Province,et al.  Tree‐based recursive partitioning methods for subdividing sibpairs into relatively more homogeneous subgroups , 2001, Genetic epidemiology.

[10]  P. Sham,et al.  Using risk calculation to implement an extended relative pair analysis , 1994, Annals of human genetics.

[11]  M. Fornage,et al.  Variation in the region of the angiotensin-converting enzyme gene influences interindividual differences in blood pressure levels in young white males. , 1998, Circulation.

[12]  Burton H. Singer,et al.  Recursive partitioning in the health sciences , 1999 .

[13]  T. Dawber,et al.  Epidemiological approaches to heart disease: the Framingham Study. , 1951, American journal of public health and the nation's health.

[14]  R. Elston,et al.  The investigation of linkage between a quantitative trait and a marker locus , 1972, Behavior genetics.

[15]  R C Elston,et al.  Linkage and association analysis of angiotensin I-converting enzyme (ACE)-gene polymorphisms with ACE concentration and blood pressure. , 2001, American journal of human genetics.

[16]  M. Province,et al.  Classification methods for confronting heterogeneity. , 2001, Advances in genetics.

[17]  L. Almasy,et al.  Multipoint quantitative-trait linkage analysis in general pedigrees. , 1998, American journal of human genetics.

[18]  W. Kannel,et al.  An investigation of coronary heart disease in families. The Framingham offspring study. , 1979, American journal of epidemiology.

[19]  R H Myers,et al.  Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study. , 1998, Circulation.

[20]  P. Allhoff,et al.  The Framingham Offspring Study , 1991 .

[21]  Mark R. Segal,et al.  Regression Trees for Censored Data , 1988 .

[22]  Anita L. DeStefano,et al.  Evidence for a Gene Influencing Blood Pressure on Chromosome 17: Genome Scan Linkage Results for Longitudinal Blood Pressure Phenotypes in Subjects From the Framingham Heart Study , 2000, Hypertension.