Document Detail


Genome-wide linkage screen for systolic blood pressure in the Veterans Administration Genetic Epidemiology Study (VAGES) of Mexican-Americans and confirmation of a major susceptibility locus on chromosome 6q14.1.
MedLine Citation:
PMID:  21293138     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Hypertension or high blood pressure is a strong correlate of diseases such as obesity and type 2 diabetes. We conducted a genome-wide linkage screen to identify susceptibility genes influencing systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Mexican-Americans from the Veterans Administration Genetic Epidemiology Study (VAGES).
METHODS: Using data from 1,089 individuals distributed across 266 families, we performed a multipoint linkage analysis to localize susceptibility loci for SBP and DBP by applying two models. In model 1, we added a sensible constant to the observed BP values in treated subjects [Tobin et al.; Stat Med 2005;24:2911-2935] to account for antihypertensive use (i.e. 15 and 10 mm Hg to SBP and DBP values, respectively). In model 2, we fixed values of 140 mm Hg for SBP and 90 mm Hg for DBP, if the treated values were less than the standard referenced treatment thresholds of 140/ 90 mm Hg for hypertensive status. However, if the observed treated BP values were found to be above these standard treatment thresholds, the actual observed treated BP values were retained in order not to reduce them by substitution of the treatment threshold values.
RESULTS: The multipoint linkage analysis revealed strong linkage signals for SBP compared with DBP. The strongest evidence for linkage of SBP (model 1, LOD = 5.0; model 2, LOD = 3.6) was found on chromosome 6q14.1 near the marker D6S1031 (89 cM) in both models. In addition, some evidence for SBP linkage occurred on chromosomes 1q, 4p, and 16p. Most importantly, our major SBP linkage finding on chromosome 6q near marker D6S1031 was independently confirmed in a Caucasian population (LOD = 3.3). In summary, our study found evidence for a major locus on chromosome 6q influencing SBP levels in Mexican-Americans.
Authors:
Sobha Puppala; Dawn K Coletta; Jennifer Schneider; Shirley L Hu; Vidya S Farook; Thomas D Dyer; Rector Arya; John Blangero; Ravindranath Duggirala; Ralph A DeFronzo; Christopher P Jenkinson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2011-02-05
Journal Detail:
Title:  Human heredity     Volume:  71     ISSN:  1423-0062     ISO Abbreviation:  Hum. Hered.     Publication Date:  2011  
Date Detail:
Created Date:  2011-04-21     Completed Date:  2011-08-04     Revised Date:  2013-01-14    
Medline Journal Info:
Nlm Unique ID:  0200525     Medline TA:  Hum Hered     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  1-10     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 S. Karger AG, Basel.
Affiliation:
Southwest Foundation for Biomedical Research, San Antonio, Texas, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Blood Pressure / genetics*
Chromosomes, Human, Pair 6 / genetics*
Female
Genetic Linkage / genetics*
Genetic Loci / genetics*
Genetic Predisposition to Disease / genetics*
Genome-Wide Association Study*
Genotype
Humans
Male
Mexican Americans / genetics*
Middle Aged
Models, Genetic
Phenotype
Systole / genetics
United States
United States Department of Veterans Affairs
Grant Support
ID/Acronym/Agency:
DK42273/DK/NIDDK NIH HHS; DK47482/DK/NIDDK NIH HHS; DK53889/DK/NIDDK NIH HHS; DK70746/DK/NIDDK NIH HHS; MH59490/MH/NIMH NIH HHS; R01 DK079195/DK/NIDDK NIH HHS
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