Genome-wide Linkage Analysis of Pulse Pressure in American Indians: The Strong Heart Study

Franceschini, Nora; MacCluer, Jean W.; Rose, Kathreen M.; Rutherford, Susan; Cole, Shelley A.; Laston, Sandy; Göring, Harald H.H.; Diego, Vincent P.; Roman, Mary J.; Lee, Elisa T.; Best, Lyle G.; Howard, Barbara V.; Fabsitz, Richard R.; North, Kari E.

doi:10.1038/ajh.2007.34

Cited by 17 publications

(9 citation statements)

References 32 publications

(30 reference statements)

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“…The genetic locus we found to be linked to carotid artery size in this study has also been shown to be associated with systolic and diastolic blood pressure in Nigerian families (35) and with body mass index in the NHLBI Family Heart Study (36). While it is possible that the attenuation of the linkage signal we observed after full covariate adjustment that included blood pressure and body size could be attributed to the association of this locus to blood pressure and body size, we did not find any linkage evidence at this locus with blood pressure or body mass index in the American Indian SHFS participants (37–39). …”

Section: Discussioncontrasting

confidence: 67%

Genome-wide linkage analysis of carotid artery lumen diameter: The strong heart family study

Bella

Cole

Laston

et al. 2013

International Journal of Cardiology

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Background A significant proportion of the variability in carotid artery lumen diameter is attributable to genetic factors. Methods Carotid ultrasonography and genotyping were performed in the 3,300 American Indian participants in the Strong Heart Family Study (SHFS) to identify chromosomal regions harboring novel genes associated with inter-individual variation in carotid artery lumen diameter. Genome-wide linkage analysis was conducted using standard variance component linkage methods, implemented in SOLAR, based on multipoint identity-by-descent matrices. Results Genome-wide linkage analysis revealed a significant evidence for linkage for a locus for left carotid artery diastolic and systolic lumen diameter in Arizona SHFS participants on chromosome 7 at 120 cM (lod=4.85 and 3.77, respectively, after sex and age adjustment, and lod=3.12 and 2.72, respectively, after adjustment for sex, age, height, weight, systolic and diastolic blood pressure, diabetes mellitus and current smoking). Other regions with suggestive evidence of linkage for left carotid artery diastolic and systolic lumen diameter was found on chromosome 12 at 153 cM (lod=2.20 and 2.60, respectively, after sex and age adjustment, and lod=2.44 and 2.16, respectively, after full covariate adjustment) in Oklahoma SHFS participants; suggestive linkage for right carotid artery diastolic and systolic lumen diameter was found on chromosome 9 at 154 cM (lod=2.72 and 3.19, respectively after sex and age adjustment, and lod=2.36 and 2.21, respectively, after full covariate adjustment) in Oklahoma SHFS participants. Conclusion We found significant evidence for loci influencing carotid artery lumen diameter on chromosome 7q and suggestive linkage on chromosomes 12q and 9q.

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Section: Discussioncontrasting

confidence: 67%

Genome-wide linkage analysis of carotid artery lumen diameter: The strong heart family study

Bella

Cole

Laston

et al. 2013

International Journal of Cardiology

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“…A recently published study has also shown linkage on chromosome 7p15 (LOD 3.3) to pulse pressure, a measure of central arterial stiffness and a predictor of cardiovascular mortality [33]. None of the genomewide association studies (GWAS) of atherosclerosis have published association with variants on chromosome 7p.…”

Section: Discussionmentioning

confidence: 99%

Neuropeptide Y Gene Polymorphisms Confer Risk of Early-Onset Atherosclerosis

et al. 2009

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Neuropeptide Y (NPY) is a strong candidate gene for coronary artery disease (CAD). We have previously identified genetic linkage to familial CAD in the genomic region of NPY. We performed follow-up genetic, biostatistical, and functional analysis of NPY in early-onset CAD. In familial CAD (GENECARD, N = 420 families), we found increased microsatellite linkage to chromosome 7p14 (OSA LOD = 4.2, p = 0.004) in 97 earliest age-of-onset families. Tagged NPY SNPs demonstrated linkage to CAD of a 6-SNP block (LOD = 1.58–2.72), family-based association of this block with CAD (p = 0.02), and stronger linkage to CAD in the earliest age-of-onset families. Association of this 6-SNP block with CAD was validated in: (a) 556 non-familial early-onset CAD cases and 256 controls (OR 1.46–1.65, p = 0.01–0.05), showing stronger association in youngest cases (OR 1.84–2.20, p = 0.0004–0.09); and (b) GENECARD probands versus non-familial controls (OR 1.79–2.06, p = 0.003–0.02). A promoter SNP (rs16147) within this 6-SNP block was associated with higher plasma NPY levels (p = 0.04). To assess a causal role of NPY in atherosclerosis, we applied the NPY1-receptor–antagonist BIBP-3226 adventitially to endothelium-denuded carotid arteries of apolipoprotein E-deficient mice; treatment reduced atherosclerotic neointimal area by 50% (p = 0.03). Thus, NPY variants associate with atherosclerosis in two independent datasets (with strong age-of-onset effects) and show allele-specific expression with NPY levels, while NPY receptor antagonism reduces atherosclerosis in mice. We conclude that NPY contributes to atherosclerosis pathogenesis.

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“…Additionally, a linkage for the right carotid artery diastolic and systolic lumen diameter was also detected on chromosome 9 at 154 cM in the Oklahoma participants [ 63 ]. Linkages of chromosome 7p19q with pulse pressure, glucose/insulin/obesity factor to chromosome 4, the dyslipidemia factor to chromosome 12, and the blood pressure factor to chromosome 1 were also identified among SHFS participants [ 64 , 65 ].…”

Section: Genetics Heritability and Other Risk Factors Contributementioning

confidence: 99%

Diabetes and Associated Cardiovascular Complications in American Indians/Alaskan Natives: A Review of Risks and Prevention Strategies

Poudel

Zhou

Story

et al. 2018

Journal of Diabetes Research

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Diabetes mellitus (DM) is the seventh leading cause of death in the United States and the leading cause of death in the U.S. American Indian/Alaskan Natives (AI/ANs), who comprise only 2% of the total population. The AI/AN population has a high prevalence of DM in adults aged 20 years or older and is developing DM at a younger age than the general U.S. population. DM is a major risk factor for cardiovascular disease (CVD), and mortality from CVD is higher in AI/ANs than the general population, as is the prevalence of stroke and 1-year poststroke mortality for both genders when compared to non-Hispanic whites. A genome-wide scan found a number of chromosome linkages in the AI/AN population that suggest that genetic factors may contribute to their high risk of DM and CVD. Importantly, studies also suggest that in addition to race/ethnicity, cultural norms and historic conditions play important roles in the prevalence of DM and CVD in this population. Therefore, multiple factors should be taken into consideration when establishing prevention programs to decrease the prevalence of obesity, diabetes, and CVD incidence among adults and children in the AI/AN population. Prevention programs should focus on behavioral risk factors and lifestyle changes like encouraging smoking cessation, healthy diet, and increased physical activity while taking into consideration cultural, economic, and geographic factors.

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Genome-wide Linkage Analysis of Pulse Pressure in American Indians: The Strong Heart Study

Abstract: The signal on 7p15.3 overlaps positive findings for pulse pressure among Utah population samples, suggesting that this region may harbor gene variants for blood pressure related traits.

Cited by 17 publications

References 32 publications

Genome-wide linkage analysis of carotid artery lumen diameter: The strong heart family study

Genome-wide linkage analysis of carotid artery lumen diameter: The strong heart family study

Neuropeptide Y Gene Polymorphisms Confer Risk of Early-Onset Atherosclerosis

Diabetes and Associated Cardiovascular Complications in American Indians/Alaskan Natives: A Review of Risks and Prevention Strategies

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