Linkage analysis of a composite factor for the multiple metabolic syndrome: the National Heart, Lung, and Blood Institute Family Heart Study.
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.
Tang
Weihong
W
Division of Epidemiology, University of Minnesota, Minneapolis 55454, USA.
Miller
Michael B
MB
Rich
Stephen S
SS
North
Kari E
KE
Pankow
James S
JS
Borecki
Ingrid B
IB
Myers
Richard H
RH
Hopkins
Paul N
PN
Leppert
Mark
M
Arnett
Donna K
DK
D001786:Blood Glucose / Q000378:metabolism; D001798:Blood Proteins / Q000032:analysis; D015992:Body Mass Index; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D009316:National Institutes of Health (U.S.); D012307:Risk Factors; D014481:United States
D001786:Blood Glucose; D001798:Blood Proteins