Genome-Wide Linkage Analysis for Loci Affecting Pulse Pressure

Bielinski, Suzette J; Lynch, Amy I.; Miller, Michael B.; Weder, Alan B.; Cooper, Richard S.; Oberman, Albert; Chen, Yii Der Ida; Turner, Stephen T.; Fornage, Myriam; Province, Michael A.; Arnett, Donna K.

doi:10.1161/01.hyp.0000191706.41980.29

Cited by 38 publications

(57 citation statements)

References 42 publications

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“…This region is where the G protein-coupled receptor gene resides, which is involved in the signaling cascades that regulate blood pressure during changes in cardiac output. 17 The highest suggestive linkage peak on chromosome 7 at 74.37 cM coincides with a linkage peak at 75 cM reported by Bielinski et al 13 and is in the vicinity of a peak at 71 cM in the same region reported by DeStefano et al 15 The peak regions on chromosomes 17 and 22 cover linkage peaks for PP reported by Bielinski et al 13 (at 89 cM on chromosome 17 and 11 cM on chromosome 22). In addition, their study also detected linkages on chromosomes 1 (106 cM), 3 (172 cM) and 7 (75 cM), which are located in the vicinity of our suggestive regions.…”

Section: Discussionsupporting

confidence: 80%

“…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. It is interesting that this is exactly the location for our linkage peak on chromosome 18 (at 70.75 cM, Figure 1).…”

Section: Discussionmentioning

confidence: 68%

“…12 The existence of a genetic contribution has warranted efforts to elucidate genes that affect PP, especially in recent years. For example, genetic marker-based linkage studies have identified multiple loci harboring susceptibility genes for PP in different populations, including Caucasians, 9,13,14 Mexicans, 15 American Indians 16 and African Americans. 17 The verification of susceptibility loci requires replication studies within and across populations to consolidate linkage results, which is especially important given the fact that inconsistent linkage results were reported by different studies.…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

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

Zhang

Pang

et al. 2012

Hypertens Res

View full text Add to dashboard Cite

show abstract

“…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. It is interesting that this is exactly the location for our linkage peak on chromosome 18 (at 70.75 cM, Figure 3).…”

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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“…Near our peak linkage signal at 17q24.2, suggestive linkage to pulse pressure was identified in Hispanics participating in the National Heart, Lung, and Blood Institute Family Blood Pressure Program (FBPP). 29 In addition, genome-wide evidence for linkage was identified at region 17q23.2 for blood pressure factor in Hispanic participants of the FBPP (LODϭ3.6). Interestingly, some evidence for linkage was also observed in white HyperGEN participants (which is 1 of the 4 networks of the FBPP) in this same region (LODϭ1.5).…”

Section: Discussionmentioning

confidence: 99%

A Quantitative Trait Loci-Specific Gene-by-Sex Interaction on Systolic Blood Pressure Among American Indians

et al. 2006

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Abstract-Age-adjusted systolic blood pressure is higher in males than females. Genetic factors may account for this sex-specific variation. To localize sex-specific quantitative trait loci (QTL) influencing blood pressure, we conducted a genome scan of systolic blood pressure, in males and females, separately and combined, and tested for aggregate and QTL-specific genotype-by-sex interaction in American Indian participants of the Strong Heart Family Study. Blood pressure was measured 3 times and the average of the last 2 measures was used for analyses. Systolic blood pressure was adjusted for age and antihypertensive treatment within study center. We performed variance component linkage analysis in the full sample and stratified by sex among 1168 females and 726 males. Marker allele frequencies were derived using maximum likelihood estimates based on all individuals, and multipoint identity-by-descent sharing was estimated using Loki. We detected suggestive evidence of a QTL influencing systolic blood pressure on chromosome 17 at 129 cM between markers D17S784 and D17S928 (logarithm of odds [LOD]ϭ2.4). This signal substantially improved when accounting for QTL-specific genotype-by-sex interaction (Pϭ0.04), because we observed an LOD score of 3.3 for systolic blood pressure in women on chromosome 17 at 136 cM. The magnitude of the linkage signal on chromosome 17q25.3 was slightly attenuated when participants taking antihypertensive medications were excluded, although suggestive evidence for linkage was still identified (LODϭ2.8 in women). Accounting for interaction with sex improved our ability to detect QTLs and demonstrated the importance of considering genotype-by-sex interaction in our search for blood pressure genes. Key Words: epidemiology Ⅲ blood pressure Ⅲ gender S exual dimorphism in the regulation of blood pressure has been demonstrated in several population studies 1-3 and in experimental animal models. 2 Age-adjusted blood pressure is consistently higher in men than women, but these differences are attenuated when women enter menopause. 1 These findings suggest the presence of distinct mechanisms of blood pressure regulation in males and females and stress the importance of the sex hormonal environment in determining blood pressure.Genetic factors account for 30% to 40% of the blood pressure variation in a population, 4 and the effect of some genes may be apparent only in the setting of appropriate sex hormonal milieu. Several genome scans of blood pressure variation have been published, but limited success has been achieved in identifying genes influencing blood pressure in the general population. One reason that few studies have identified significant linkage to blood pressure variation may be genotype-by-sex interaction, which, when present, could reduce the power to localize quantitative trait loci (QTL). Indeed, none of the previous gene mapping studies have accounted for genotype-by-sex interaction on blood pressure variation. In this article, we examine the evidence for genotype-by-sex interact...

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Genome-Wide Linkage Analysis for Loci Affecting Pulse Pressure

Cited by 38 publications

References 42 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

A Quantitative Trait Loci-Specific Gene-by-Sex Interaction on Systolic Blood Pressure Among American Indians

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