Genome-Wide Multipoint Parametric Linkage Analysis of Pulse Pressure in Large, Extended Utah Pedigrees

Camp, Nicola J.; Hopkins, Paul N.; Hasstedt, Sandra J.; Coon, Hilary; Malhotra, Alka; Cawthon, Richard M.; Hunt, Steven C.

doi:10.1161/01.hyp.0000084874.85653.46

Cited by 46 publications

(57 citation statements)

References 55 publications

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“…It is surprising that among the three significant linkage peaks, two have been confirmed to show linkage in other populations. In a multipoint linkage scan performed on large and extended Utah pedigrees, Camp et al 31 reported linkage evidence on chromosome 12q at 109 cM, which is covered by our linkage region on chromosome 12 in Figure 1. In another study based on American families, Bielinski et al 13 detected a significant linkage for PP on chromosome 18 at 71 cM; this was the most significant linkage in their study.…”

Section: Discussionmentioning

confidence: 74%

Genome-wide linkage and association scans for pulse pressure in Chinese twins

Zhang

Pang

et al. 2012

Hypertens Res

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Elevated pulse pressure (PP) is associated with cardiovascular disorders and mortality in various populations. The genetic influence on PP has been confirmed by heritability estimates using related individuals. Recently, efforts have been made by mapping genes that are linked to the phenotype. We report the results of our gene mapping studies conducted in the Chinese population in mainland China. The genome-wide linkage and association scans were carried out on 63 middle-aged dizygotic twin pairs using high-density markers. The linkage analysis identified three significant linkage peaks (all with a single point Po1e À05 ) on chromosome 11 (LOD core 4.06 at 30.5 cM), chromosome 12 (LOD score 3.97 at 100.7 cM) and chromosome 18 (LOD score 4.01 at 70.7 cM), with the last two peaks closely overlapping with linkage peaks reported by two American studies. Multiple regions with suggestive linkages were identified, with many of the peaks overlapping with published linkage regions. The genome-wide association analysis detected a suggestive association on chromosome 4 (rs17031508, Po8.34e À08 ) located within a wide region of suggestive linkage. Our results provide some evidence for genetic linkages and associations with PP in the Chinese population. Further investigation is warranted to replicate the findings and to explore the susceptibility loci or genes for PP.

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Section: Discussionmentioning

confidence: 74%

Genome-wide linkage and association scans for pulse pressure in Chinese twins

Zhang

Pang

et al. 2012

Hypertens Res

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“…It is surprising that among the three significant linkage peaks, two have been confirmed to show linkage in other populations. In a multipoint linkage scan performed on large and extended Utah pedigrees, Camp et al (2003) reported linkage evidence on chromosome 12q at 109 cM which is covered by our linkage region on chromosome 12 in Figure 3. In another study based on American families, Bielinski et al (2005) detected a significant linkage for PP on chromosome 18 at 71 cM, the most significant linkage in their study.…”

Section: Figurementioning

confidence: 83%

Heritability and Whole Genome Linkage of Pulse Pressure in Chinese Twin Pairs

et al. 2012

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Elevated pulse pressure is associated with cardiovascular disorders and mortality in various populations. The genetic influence on pulse pressure has been confirmed by heritability estimates using related individuals. Recently, efforts have been made in mapping genes that are linked to the phenotype. We report results on our heritability and linkage study conducted on the Chinese population in mainland China where cardiovascular and cerebrovascular diseases are becoming the leading cause of death. A total of 630 pairs of middle-aged Chinese twins were collected for heritability analysis, from which 63 dizygotic twin pairs were randomly selected for genome-wide linkage analysis using Affymetrix 6.0 SNP array. Regression analysis reconfirmed the significant effects of age, sex, and BMI on pulse pressure. Comparison of twin models suggested the parsimonious AE model as the best model with a heritability estimate of 0.45. Genome-wide non-parametric linkage analysis identified three significant linkage peaks on chromosome 11 (lod score 4.06 at 30.5 cM), chromosome 12 (lod score 3.97 at 100.7 cM), and chromosome 18 (lod score 4.01 at 70.7 cM) with the last two peaks closely overlapping with linkage peaks reported by two American studies. In addition, multiple regions with suggestive linkage were identified with many of them overlapping with published linkage regions. Our results provide both epidemiological and molecular genetic evidence for the genetic dissection of pulse pressure in the Chinese population, which could help in fine mapping and in characterizing genes that are involved in the regulation of pulse pressure.

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“…How- ever, in our Utah pedigrees, we did not see evidence for linkage of blood pressure or pulse pressure in this chromosomal region. 10 Logarithm of odds scores were Ͻ0.6 for every marker in the region for SBP, DBP, and pulse pressure. This illustrates that lack of linkage does not rule out significant associations of genes in a particular region with phenotypes of interest.…”

Section: Discussionmentioning

confidence: 99%

Sodium Bicarbonate Cotransporter Polymorphisms Are Associated With Baseline and 10-Year Follow-Up Blood Pressures

Hunt

Xin

et al. 2006

Hypertension

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Abstract-The NaHCO 3 cotransporter gene (SLC4A5) on chromosome 2 encodes a protein that transports sodium and bicarbonate across the cell membrane and regulates cellular pH. The National Heart, Lung, and Blood Institute Family Blood Pressure Program found linkage of blood pressure-related traits to the chromosomal region containing SLC4A5 and phenotype associations with single nucleotide polymorphisms (SNPs) in this gene. However, the results were inconsistent over various phenotypes and SNPs. Nevertheless, the evidence was strong enough to propose this gene as a blood pressure-related gene. To extend these findings, SLC4A5 SNPs were genotyped in an independent set of 96 Utah pedigrees of 1040 adult subjects at baseline, 760 of whom were followed longitudinally for 10 years. After adjusting for age, gender, body mass index, and polygenic correlations within pedigrees, SNP hcv1137534 was significantly associated with both systolic blood pressure and diastolic blood pressure (DBP) at baseline (unadjusted Pϭ0.009 and Pϭ0.043; respectively) and at 10-year follow-up (Pϭ0.008 and Pϭ0.007; respectively). In secondary tests of association of baseline-stressed blood pressure, hcv1137534 was borderline or significantly associated with DBP change during an isometric handgrip test (Pϭ0.054), DBP change from supine to standing (Pϭ0.020), and DBP change after a 50°tilt (Pϭ0.034). There was no evidence for compensation of abnormal SLC4A5 sodium transport by genotype-specific differences in sodium-lithium countertransport, lithium-potassium cotransport, altered plasma sodium, chloride, or CO 2 levels. Therefore, in these Utah pedigrees, the SLC4A5 gene was significantly associated with blood pressure and persisted after 10 years of follow-up. These results additionally confirm the involvement of SLC4A5 with blood pressure control, although the mechanism is still unclear.

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Genome-Wide Multipoint Parametric Linkage Analysis of Pulse Pressure in Large, Extended Utah Pedigrees

Cited by 46 publications

References 55 publications

Genome-wide linkage and association scans for pulse pressure in Chinese twins

Genome-wide linkage and association scans for pulse pressure in Chinese twins

Heritability and Whole Genome Linkage of Pulse Pressure in Chinese Twin Pairs

Sodium Bicarbonate Cotransporter Polymorphisms Are Associated With Baseline and 10-Year Follow-Up Blood Pressures

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