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Diabetes 52:2840-2847, 2003
© 2003 by the American Diabetes Association, Inc.

Linkage Analysis of a Composite Factor for the Multiple Metabolic Syndrome

The National Heart, Lung, and Blood Institute Family Heart Study

Weihong Tang1, Michael B. Miller1, Stephen S. Rich2, Kari E. North3, James S. Pankow1, Ingrid B. Borecki4, Richard H. Myers5, Paul N. Hopkins6, Mark Leppert7, and Donna K. Arnett1

1 Division of Epidemiology, University of Minnesota, Minneapolis, Minnesota
2 Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina
3 Department of Epidemiology, University of North Carolina Chapel Hill, Chapel Hill, North Carolina
4 Division of Biostatistics and Department of Genetics, Washington University School of Medicine, St. Louis, Missouri
5 Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts
6 Cardiovascular Genetics, University of Utah, Salt Lake City, Utah
7 Human Genetics, University of Utah, Salt Lake City, Utah

Recent studies have demonstrated significant genetic and phenotypic correlation underlying the clustering of traits involved in the multiple metabolic syndrome (MMS). The aim of this study was to identify chromosomal regions contributing to MMS-related traits represented by composite factors derived from factor analysis. Data from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study were subjected to a maximum likelihood–based factor analysis. These analyses generated an MMS factor that was loaded by BMI, waist-to-hip ratio, subscapular skinfold, triglycerides, HDL, homeostasis model assessment index, plasminogen activator inhibitor-1 antigen, and serum uric acid. Genetic data were obtained for 2,467 subjects from 387 three-generation families (402 markers, the NHLBI Mammalian Genotyping Service) and 1,082 subjects from 256 sibships (243 markers, the Utah Molecular Genetics Laboratory). Multipoint variance components linkage analysis (GENEHUNTER version 2.1) of the MMS factor was conducted in the combined marker set sample. The greatest evidence for linkage was found on chromosome 2, with a peak LOD of 3.34 at 240 cM. Suggestive linkage was also observed for regions on chromosomes 7, 12, 14, and 15. In summary, a genomic region on chromosome 2 may contain a pleiotropic locus contributing to the clustering of MMS-related phenotypes.

Address correspondence and reprint requests to Donna K. Arnett, University of Minnesota, Division of Epidemiology, 1300 South Second St., Suite 300, Minneapolis, MN 55454. E-mail: arnett{at}epi.umn.edu


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