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

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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalHuman Heredity
Volume71
Issue number1
DOIs
StatePublished - Apr 2011

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United States Department of Veterans Affairs
Molecular Epidemiology
Chromosomes
Genome
Blood Pressure

Keywords

  • Antihypertensive medication
  • Genetic location
  • Heritability
  • Hypertension
  • Linkage

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

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. / Puppala, Sobha; Coletta, Dawn K.; Schneider, Jennifer; Hu, Shirley L.; Farook, Vidya S.; Dyer, Thomas D.; Arya, Rector; Blangero, John; Duggirala, Ravindranath; Defronzo, Ralph A.; Jenkinson, Christopher P.

In: Human Heredity, Vol. 71, No. 1, 04.2011, p. 1-10.

Research output: Contribution to journalArticle

Puppala, S, Coletta, DK, Schneider, J, Hu, SL, Farook, VS, Dyer, TD, Arya, R, Blangero, J, Duggirala, R, Defronzo, RA & Jenkinson, CP 2011, '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', Human Heredity, vol. 71, no. 1, pp. 1-10. https://doi.org/10.1159/000323143
Puppala, Sobha ; Coletta, Dawn K. ; Schneider, Jennifer ; Hu, Shirley L. ; Farook, Vidya S. ; Dyer, Thomas D. ; Arya, Rector ; Blangero, John ; Duggirala, Ravindranath ; Defronzo, Ralph A. ; Jenkinson, Christopher P. / 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. In: Human Heredity. 2011 ; Vol. 71, No. 1. pp. 1-10.
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abstract = "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.",
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AU - Puppala, Sobha

AU - Coletta, Dawn K.

AU - Schneider, Jennifer

AU - Hu, Shirley L.

AU - Farook, Vidya S.

AU - Dyer, Thomas D.

AU - Arya, Rector

AU - Blangero, John

AU - Duggirala, Ravindranath

AU - Defronzo, Ralph A.

AU - Jenkinson, Christopher P.

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AB - 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.

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KW - Genetic location

KW - Heritability

KW - Hypertension

KW - Linkage

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