Dataset Information

Social- and behavioral-specific genetic effects on blood pressure traits: the Strong Heart Family Study.

ABSTRACT: Population studies have demonstrated an important role of social, behavioral, and environmental factors in blood pressure (BP) levels. Accounting for the genetic interaction of these factors may help to identify common BP susceptibility alleles.We studied the interaction of additive genetic effects and behavioral (physical activity, smoking, alcohol use) and socioeconomic (education) factors on BP in approximately 3600 American Indian participants of the Strong Heart Family Study, using variance component models. The mean and SD of resting systolic and diastolic BPs were 123 + or - 17 and 76 + or - 11 mm Hg, respectively. We detected evidence for distinct genetic effects on diastolic BP among ever smokers compared with never smokers (P = 0.01). For alcohol intake, we observed significant genotype-by-environment interactions on diastolic (rhog = 0.10, P = 0.0003) and on systolic BPs (rhog = 0.59, P = 0.0008) among current drinkers compared with former or never drinkers. We also detected genotype-by-physical activity interactions on diastolic BP (rhog = 0.35, P = 0.0004). Finally, there was evidence for distinct genetic effects on diastolic BP among individuals with less than high school education compared with those with 12 or more years of education (rhog = 0.41, P = 0.02).Our findings suggest that behavioral and socioeconomic factors can modify the genetic effects on BP phenotypes. Accounting for context dependent factors may help us to better understand the complexities of the gene effects on BP and other complex phenotypes with high levels of genetic heterogeneity.

SUBMITTER: Franceschini N

PROVIDER: S-EPMC2742382 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Social- and behavioral-specific genetic effects on blood pressure traits: the Strong Heart Family Study.

Franceschini Nora N Rose Kathryn M KM Storti Kristi L KL Rutherford Sue S Voruganti V Saroja VS Laston Sandy S Göring Harald H H HH Dyer Thomas D TD Umans Jason G JG Lee Elisa T ET Best Lyle G LG Fabsitz Richard R RR Cole Shelley A SA MacCluer Jean W JW North Kari E KE

Circulation. Cardiovascular genetics 20090616 4

<h4>Background</h4>Population studies have demonstrated an important role of social, behavioral, and environmental factors in blood pressure (BP) levels. Accounting for the genetic interaction of these factors may help to identify common BP susceptibility alleles.<h4>Methods and results</h4>We studied the interaction of additive genetic effects and behavioral (physical activity, smoking, alcohol use) and socioeconomic (education) factors on BP in approximately 3600 American Indian participants o ...[more]

PMID: 20031612

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Project description:Background: Increased serum levels of C-reactive protein (CRP), an important component of the innate immune response, are associated with increased risk of cardiovascular disease (CVD). Multiple single nucleotide polymorphisms (SNP) have been identified which are associated with CRP levels, and Mendelian randomization studies have shown a positive association between SNPs increasing CRP expression and risk of colon cancer (but thus far not CVD). The effects of individual genetic variants often interact with the genetic background of a population and hence we sought to resolve the genetic determinants of serum CRP in a number of American Indian populations.Methods: The Strong Heart Family Study (SHFS) has serum CRP measurements from 2428 tribal members, recruited as large families from three regions of the United States. Microsatellite markers and MetaboChip defined SNP genotypes were incorporated into variance components, decomposition-based linkage and association analyses.Results: CRP levels exhibited significant heritability (h2 = 0.33 ± 0.05, p<1.3 X 10-20). A locus on chromosome (chr) 6, near marker D6S281 (approximately at 169.6 Mb, GRCh38/hg38) showed suggestive linkage (LOD = 1.9) to CRP levels. No individual SNPs were found associated with CRP levels after Bonferroni adjustment for multiple testing (threshold <7.77 x 10-7), however, we found nominal associations, many of which replicate previous findings at the CRP, HNF1A and 7 other loci. In addition, we report association of 46 SNPs located at 7 novel loci on chromosomes 2, 5, 6(2 loci), 9, 10 and 17, with an average of 15.3 Kb between SNPs and all with p-values less than 7.2 X 10-4.Conclusion: In agreement with evidence from other populations, these data show CRP serum levels are under considerable genetic influence; and include loci, such as near CRP and other genes, that replicate results from other ethnic groups. These findings also suggest possible novel loci on chr 6 and other chromosomes that warrant further investigation.

Project description:Background: Genetic research may inform underlying mechanisms for disparities in the burden of type 2 diabetes mellitus among American Indians. Our objective was to assess the association of genetic variants in cardiometabolic candidate genes with B cell dysfunction via HOMA-B, insulin resistance via HOMA-IR, and type 2 diabetes mellitus in the Strong Heart Family Study (SHFS). Methods and Results: We examined the association of variants, previously associated with cardiometabolic traits (?200,000 from Illumina Cardio MetaboChip), using mixed models of HOMA-B residuals corrected for HOMA-IR (cHOMA-B), log transformed HOMA-IR, and incident diabetes, adjusted for age, sex, population stratification, and familial relatedness. Center-specific estimates were combined using fixed effect meta-analyses. We used Bonferroni correction to account for multiple testing (P < 4.13 × 10-7). We also assessed the association between variants in candidate diabetes genes with these metabolic traits. We explored the top SNPs in an independent, replication sample from Southwestern Arizona. We identified significant associations with cHOMA-B for common variants at 26 loci of which 8 were novel (PRSS7, FCRL5, PEL1, LRP12, IGLL1, ARHGEF10, PARVA, FLJ16686). The most significant variant association with cHOMA-B was observed on chromosome 5 for an intergenic variant near PARP8 (rs2961831, P = 6.39 × 10-9). In the replication study, we found a signal at rs4607517 near GCK/YKT6 (P = 0.01). Variants near candidate diabetes genes (especially GCK and KCNQ1) were also nominally associated with HOMA-IR and cHOMA-B. Conclusion: We identified variants at novel loci and confirmed those at known candidate diabetes loci associations for cHOMA-B. This study also provided evidence for association of variants at KCNQ2, CTNAA2, and KCNQ1with cHOMA-B among American Indians. Further studies are needed to account for the high heritability of diabetes among the American Indian participants of the SHFS cohort.

Dataset Information

Social- and behavioral-specific genetic effects on blood pressure traits: the Strong Heart Family Study.

Publications

Social- and behavioral-specific genetic effects on blood pressure traits: the Strong Heart Family Study.

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