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Empirically derived phenotypic subgroups - qualitative and quantitative trait analyses.

Marsha A Wilcox¹, Diego F Wyszynski, Carolien I Panhuysen

¹Genetics Program, Department of Medicine, Boston University School of Medicine, 715 Albany Street, Boston, Massachusetts 02118, USA. mwilcox@bu.edu

|February 21, 2004

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This study identified four distinct groups from Framingham Heart Study data, with one heritable group exhibiting atherogenic dyslipidemia. Genetic linkage analysis revealed potential novel loci for complex traits.

Area of Science:

Genetics
Biostatistics
Cardiovascular Medicine

Background:

The Framingham Heart Study has historically focused on univariate phenotypes.
Understanding complex traits requires exploring multivariate approaches.

Purpose of the Study:

To derive multivariate traits by identifying homogeneous groups.
To assess the heritability of these derived traits.
To conduct linkage analysis on a heritable trait.

Main Methods:

Multiple correspondence analysis for data reduction.
Two-stage clustering (k-means and hierarchical) for group identification.
SOLAR for heritability and quantitative trait analysis, GENEHUNTER-PLUS for qualitative trait analysis.

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Main Results:

Four distinct phenotypic groups were identified.
One group, characterized by atherogenic dyslipidemia, showed significant heritability (38%, p < 1 x 10(-6)).
Linkage analysis identified significant LOD scores on chromosomes 11 and 14, with suggestive findings on chromosomes 6 and 11.

Conclusions:

This multivariate approach aids in defining complex phenotypes for genetic analysis.
Findings suggest potential genetic loci for atherogenic dyslipidemia and related conditions.
Some results may represent novel findings or require further validation.