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Articles by R. R Fabsitz
Total Records ( 2 ) for R. R Fabsitz
  N Franceschini , K. M Rose , K. L Storti , S Rutherford , V. S Voruganti , S Laston , H. H.H Goring , T. D Dyer , J. G Umans , E. T Lee , L. G Best , R. R Fabsitz , S. A Cole , J. W MacCluer and K. E. North

Background— 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.

Methods and Results— We studied the interaction of additive genetic effects and behavioral (physical activity, smoking, alcohol use) and socioeconomic (education) factors on BP in 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±17 and 76±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 (g=0.10, P=0.0003) and on systolic BPs (g=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 (g=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 (g=0.41, P=0.02).

Conclusions— 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.

  K Musunuru , G Lettre , T Young , D. N Farlow , J. P Pirruccello , K. G Ejebe , B. J Keating , Q Yang , M. H Chen , N Lapchyk , A Crenshaw , L Ziaugra , A Rachupka , E. J Benjamin , L. A Cupples , M Fornage , E. R Fox , S. R Heckbert , J. N Hirschhorn , C Newton Cheh , M. M Nizzari , D. N Paltoo , G. J Papanicolaou , S. R Patel , B. M Psaty , D. J Rader , S Redline , S. S Rich , J. I Rotter , H. A Taylor , R. P Tracy , R. S Vasan , J. G Wilson , S Kathiresan , R. R Fabsitz , E Boerwinkle , S. B Gabriel and for the NHLBI Candidate Gene Association Resource

The National Heart, Lung, and Blood Institute's Candidate Gene Association Resource (CARe), a planned cross-cohort analysis of genetic variation in cardiovascular, pulmonary, hematologic, and sleep-related traits, comprises >40 000 participants representing 4 ethnic groups in 9 community-based cohorts. The goals of CARe include the discovery of new variants associated with traits using a candidate gene approach and the discovery of new variants using the genome-wide association mapping approach specifically in African Americans.

Methods and Results—

CARe has assembled DNA samples for >40 000 individuals self-identified as European American, African American, Hispanic, or Chinese American, with accompanying data on hundreds of phenotypes that have been standardized and deposited in the CARe Phenotype Database. All participants were genotyped for 7 single-nucleotide polymorphisms (SNPs) selected based on prior association evidence. We performed association analyses relating each of these SNPs to lipid traits, stratified by sex and ethnicity, and adjusted for age and age squared. In at least 2 of the ethnic groups, SNPs near CETP, LIPC, and LPL strongly replicated for association with high-density lipoprotein cholesterol concentrations, PCSK9 with low-density lipoprotein cholesterol levels, and LPL and APOA5 with serum triglycerides. Notably, some SNPs showed varying effect sizes and significance of association in different ethnic groups.


The CARe Pilot Study validates the operational framework for phenotype collection, SNP genotyping, and analytic pipeline of the CARe project and validates the planned candidate gene study of 2000 biological candidate loci in all participants and genome-wide association study in 8000 African American participants. CARe will serve as a valuable resource for the scientific community.

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