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(Hypertension. 2005;46:751.)
© 2005 American Heart Association, Inc.

Original Articles

Two Major QTLs and Several Others Relate to Factors of Metabolic Syndrome in the Family Blood Pressure Program

Aldi T. Kraja; Dabeeru C. Rao; Alan B. Weder; Richard Cooper; J. David Curb; Craig L. Hanis; Stephen T. Turner; Mariza de Andrade; Chao Agnes Hsiung; Thomas Quertermous; Xiaofeng Zhu; Michael A. Province

From the Division of Biostatistics (A.T.K., D.C.R., M.A.P.), Washington University School of Medicine, St. Louis, Mo; University of Michigan Hospitals (A.B.W.), Ann Arbor, Mich; Loyola University Medical Center (R.C., X.Z.), Maywood, Ill; Pacific Health Research Institute (J.D.C.), Honolulu, Hi; Human Genetics Center (C.L.H.), University of Texas-Houston Health Science Center, Houston, Tex; Mayo Clinic (S.T.T.), College of Medicine, Rochester, Minn; Mayo Clinic (M.d.A.), Division of Biostatistics, Rochester, Minn; National Health Research Institutes (C.A.H.), Division of Biostatistics, Taipei, Taiwan; Stanford University School of Medicine (T.Q.), Stanford, Calif.

Correspondence to Aldi Kraja, DSc, PhD, Division of Biostatistics, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO 63123. E-mail aldi{at}wustl.edu

Genome-wide variance components linkage analysis was performed on 4 latent factors underlying metabolic syndrome derived from 10 risk factors. The latent factors represent obesity and insulin, blood pressure, lipids and insulin, and central obesity. The metabolic syndrome factor scores were derived in 4 ethnic groups recruited in 3 Networks of the Family Blood Pressure Program: GENOA (blacks, Hispanics, and whites), HyperGEN (blacks and whites), SAPPHIRe (Asians). Heritabilities of metabolic syndrome factors ranged from 66% for obesity and insulin to 11% for blood pressure factor. We observed higher heritabilities for obesity and insulin, and lipids and insulin, whereas those for blood pressure and central obesity were smaller. Linkage analysis detected two major quantitative trait loci. One of them linked to the obesity and insulin factor with a lod score of 3.94 (P=0.00001, marker GATA11A06, D18S53, 41.24 cM) at marker positions linkage (lod 4.71, at 46.84 cM at 1-cM-apart distances linkage), located on chromosome 18p11.21 in GENOA black. The other linked to the blood pressure factor with a lod score of 3.22 (P=0.000059, marker GATA49C09, D17S1290, 82 cM) at marker positions linkage (lod 3.56, at 84.63 cM for 1 cM apart distances linkage) located on chromosome 17q23.1 in Hispanics. These quantitative trait loci, together with 4 additional ones with lod scores >2.5, and 30 additional ones with lod score >1.7, offer hope for dissecting the genetic architecture of metabolic syndrome with beneficial implications for molecular diagnosis, prognosis, and in potential medical intervention.

Key Words: blood pressure • insulin • lipids • metabolic syndrome • obesity

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