Key result
Plasma AGT levels demonstrated high heritability (0.74, P<0.01) in 41 families, with a three-way haplotype model producing a LOD score of 5.1, though AGT did not correlate with blood pressure.
Why the study?
Does genetic variation in the AGT gene correlate with plasma AGT levels and blood pressure in UGRP families?
Observational (n=424)
Does genetic variation in the AGT gene correlate with plasma AGT levels and blood pressure in UGRP families?
Answers are grounded in this paper and cite their sources.
Genetic variation at the AGT locus accounts for a large percentage of the heritability of plasma AGT, although plasma AGT levels do not correlate with blood pressure in predominantly normotensive individuals.
BACKGROUND: Much remains unknown about the genetic factors that contribute to essential hypertension. The Utah Genetic Reference Project (UGRP) large pedigree collection provides new opportunities to study quantitative relationships between genetic variation, endophenotypes, and blood pressure. METHODS: We analyzed the relationship between common single-nucleotide polymorphisms (SNPs) and haplotypes spanning the angiotensinogen (AGT) gene and promoter region, plasma AGT levels, and systolic (SBP) and diastolic blood pressure (DBP) in 424 individuals from 41 two-generation UGRP families. RESULTS: Plasma AGT levels are significantly correlated among UGRP family members. Correlations are higher for males than for females. Parent-offspring correlations for plasma AGT (0.30) are higher than those for SBP (0.26) and DBP (0.17) (all P values <0.01). The additive heritability (h(2)) for plasma AGT is high (0.74) and substantially exceeds heritability estimates for SBP (0.26) and DBP (0.16) (all P values <0.01). Significant linkage (logarithm of the odds (LOD) >3) is found between six AGT SNPs and plasma AGT. A model that utilizes three AGT haplotype groups produces the best LOD score (5.1) that exceeds the best single SNP LOD score (3.8). Plasma AGT and blood pressure were not significantly correlated. CONCLUSIONS: Plasma AGT levels demonstrate high heritability in 41 UGRP families. Locus-specific heritability estimates for AGT SNPs and haplotypes approach 67%, indicating that variation at AGT accounts for a large percentage of the heritability of plasma AGT. A three-way haplotype model outperforms single SNPs for quantitative linkage analysis to plasma AGT. In these predominantly normotensive individuals, plasma AGT did not correlate significantly with blood pressure.
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Watkins et al. (2010) conducted an observational in Essential hypertension (n=424). AGT genetic variation (SNPs and haplotypes) was evaluated on Heritability of plasma AGT and its correlation with blood pressure (h(2) 0.74, p=<0.01). Plasma AGT levels demonstrated high heritability (0.74, P<0.01) in 41 families, with a three-way haplotype model producing a LOD score of 5.1, though AGT did not correlate with blood pressure.
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