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

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 46; no. 4; pp. 751 - 758
• Main Authors: Kraja, Aldi T, Rao, Dabeeru C, Weder, Alan B, Cooper, Richard, Curb, J David, Hanis, Craig L, Turner, Stephen T, de Andrade, Mariza, Hsiung, Chao Agnes, Quertermous, Thomas, Zhu, Xiaofeng, Province, Michael A
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01-10-2005; Hagerstown, MD Lippincott
• Subjects: African Continental Ancestry Group - genetics; Arterial hypertension. Arterial hypotension; Asian Continental Ancestry Group - genetics; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - genetics; Cardiology. Vascular system; Chromosomes, Human, Pair 17; Chromosomes, Human, Pair 18; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Databases, Factual; European Continental Ancestry Group - genetics; Factor Analysis, Statistical; Fundamental and applied biological sciences. Psychology; Genetic Linkage; Genetic Predisposition to Disease; Hemodynamics. Rheology; Hispanic Americans - genetics; Humans; Insulin - blood; Lipids - blood; Lod Score; Medical sciences; Metabolic Syndrome - ethnology; Metabolic Syndrome - genetics; Obesity - genetics; Quantitative Trait Loci; Vertebrates: cardiovascular system; Obesity; lipids; Prognosis; Nutrition disorder; Chromosome; Insulin; Ethnic group; metabolic syndrome; Risk factor; Genetic linkage; Arterial pressure; Blood pressure; Diagnosis; Genome; Nutritional status
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.0000184249.20016.bb

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 ProgramGENOA (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.