Empirically Derived Phenotypic Subgroups – Qualitative and Quantitative Trait Analyses
Wilcox, Marsha A.
Wyszynski, Diego F.
Panhuysen, Carolien I.
Farrer, Lindsay A.
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CitationWilcox, Marsha A, Diego F Wyszynski, Carolien I Panhuysen, Qianli Ma, Agustin Yip, John Farrell, Lindsay A Farrer. "Empirically derived phenotypic subgroups – qualitative and quantitative trait analyses" BMC Genetics 4(Suppl 1):S15. (2003)
BACKGROUND. The Framingham Heart Study has contributed a great deal to advances in medicine. Most of the phenotypes investigated have been univariate traits (quantitative or qualitative). The aims of this study are to derive multivariate traits by identifying homogeneous groups of people and assigning both qualitative and quantitative trait scores; to assess the heritability of the derived traits; and to conduct both qualitative and quantitative linkage analysis on one of the heritable traits. METHODS. Multiple correspondence analysis, a nonparametric analogue of principal components analysis, was used for data reduction. Two-stage clustering, using both k-means and agglomerative hierarchical clustering, was used to cluster individuals based upon axes (factor) scores obtained from the data reduction. Probability of cluster membership was calculated using binary logistic regression. Heritability was calculated using SOLAR, which was also used for the quantitative trait analysis. GENEHUNTER-PLUS was used for the qualitative trait analysis. RESULTS. We found four phenotypically distinct groups. Membership in the smallest group was heritable (38%, p < 1 × 10-6) and had characteristics consistent with atherogenic dyslipidemia. We found both qualitative and quantitative LOD scores above 3 on chromosomes 11 and 14 (11q13, 14q23, 14q31). There were two Kong & Cox LOD scores above 1.0 on chromosome 6 (6p21) and chromosome 11 (11q23). CONCLUSION. This approach may be useful for the identification of genetic heterogeneity in complex phenotypes by clarifying the phenotype definition prior to linkage analysis. Some of our findings are in regions linked to elements of atherogenic dyslipidemia and related diagnoses, some may be novel, or may be false positives.
RightsCopyright 2003 Wilcox et al; licensee BioMed Central Ltd 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.
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