Mapping of a blood pressure QTL on chromosome 17 in American Indians of the strong heart family study

Nora Franceschini, Ran Tao, Lan Liu, Sue Rutherford, Karin Haack, Laura Almasy, Harald H H Göring, Sandra Laston, Elisa T. Lee, Lyle G. Best, Richard Fabsitz, Shelley A. Cole, Kari E. North

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Blood pressure (BP) is a complex trait, with a heritability of 30 to 40%. Several genome wide associated BP loci explain only a small fraction of the phenotypic variation. Family studies can provide an important tool for gene discovery by utilizing trait and genetic transmission information among relative-pairs. We have previously described a quantitative trait locus at chromosome 17q25.3 influencing systolic BP in American Indians of the Strong Heart Family Study (SHFS). This locus has been reported to associate with variation in BP traits in family studies of Europeans, African Americans and Hispanics. Methods: To follow-up persuasive linkage findings at this locus, we performed comprehensive genotyping in the 1-LOD unit support interval region surrounding this QTL using a multi-step strategy. We first genotyped 1,334 single nucleotide polymorphisms (SNPs) in 928 individuals from families that showed evidence of linkage for BP. We then genotyped a second panel of 306 SNPs in all SHFS participants (N = 3,807) for genes that displayed the strongest evidence of association in the region, and, in a third step, included additional genotyping to better cover the genes of interest and to interrogate plausible candidate genes in the region. Results: Three genes had multiple SNPs marginally associated with systolic BP (TBC1D16, HRNBP3 and AZI1). In BQTN analysis, used to estimate the posterior probability that any variant in each gene had an effect on the phenotype, AZI1 showed the most prominent findings (posterior probability of 0.66). Importantly, upon correction for multiple testing, none of our study findings could be distinguished from chance. Conclusion: Our findings demonstrate the difficulty of follow-up studies of linkage studies for complex traits, particularly in the context of low powered studies and rare variants underlying linkage peaks.

Original languageEnglish (US)
Article number158
JournalBMC Cardiovascular Disorders
Volume14
Issue number1
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Chromosomes, Human, Pair 17
North American Indians
Blood Pressure
Single Nucleotide Polymorphism
Genes
Quantitative Trait Loci
Genetic Association Studies
Hispanic Americans
African Americans
Chromosomes
Genome
Phenotype

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Franceschini, N., Tao, R., Liu, L., Rutherford, S., Haack, K., Almasy, L., ... North, K. E. (2014). Mapping of a blood pressure QTL on chromosome 17 in American Indians of the strong heart family study. BMC Cardiovascular Disorders, 14(1), [158]. https://doi.org/10.1186/1471-2261-14-158

Mapping of a blood pressure QTL on chromosome 17 in American Indians of the strong heart family study. / Franceschini, Nora; Tao, Ran; Liu, Lan; Rutherford, Sue; Haack, Karin; Almasy, Laura; Göring, Harald H H; Laston, Sandra; Lee, Elisa T.; Best, Lyle G.; Fabsitz, Richard; Cole, Shelley A.; North, Kari E.

In: BMC Cardiovascular Disorders, Vol. 14, No. 1, 158, 2014.

Research output: Contribution to journalArticle

Franceschini, N, Tao, R, Liu, L, Rutherford, S, Haack, K, Almasy, L, Göring, HHH, Laston, S, Lee, ET, Best, LG, Fabsitz, R, Cole, SA & North, KE 2014, 'Mapping of a blood pressure QTL on chromosome 17 in American Indians of the strong heart family study', BMC Cardiovascular Disorders, vol. 14, no. 1, 158. https://doi.org/10.1186/1471-2261-14-158
Franceschini, Nora ; Tao, Ran ; Liu, Lan ; Rutherford, Sue ; Haack, Karin ; Almasy, Laura ; Göring, Harald H H ; Laston, Sandra ; Lee, Elisa T. ; Best, Lyle G. ; Fabsitz, Richard ; Cole, Shelley A. ; North, Kari E. / Mapping of a blood pressure QTL on chromosome 17 in American Indians of the strong heart family study. In: BMC Cardiovascular Disorders. 2014 ; Vol. 14, No. 1.
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AU - Rutherford, Sue

AU - Haack, Karin

AU - Almasy, Laura

AU - Göring, Harald H H

AU - Laston, Sandra

AU - Lee, Elisa T.

AU - Best, Lyle G.

AU - Fabsitz, Richard

AU - Cole, Shelley A.

AU - North, Kari E.

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