Bivariate genetic association of KIAA1797 with heart rate in American Indians: The Strong Heart Family Study

Phillip E. Melton, Susan Rutherford Siegel, Venkata Saroja Voruganti, Harald H.H. Göring, Sandra Laston, Karin Haack, Anthony G. Comuzzie, Thomas D. Dyer, Matthew P. Johnson, Jack W. Kent, Joanne E. Curran, Eric K. Moses, John Blangero, Ana Barac, Elisa T. Lee, Lyle G. Best, Richard R. Fabsitz, Richard B. Devereux, Peter M. Okin, Jonathan N. BellaUli Broeckel, Barbara V. Howard, Jean W. MacCluer, Shelley A. Cole, Laura Almasy

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Heart rate (HR) has been identified as a risk factor for cardiovascular disease (CVD), yet little is known regarding genetic factors influencing this phenotype. Previous research in American Indians (AIs) from the Strong Heart Family Study (SHFS) identified a significant quantitative trait locus (QTL) for HR on chromosome 9p21. Genetic association on HR was conducted in the SHFS. HR was measured from electrocardiogram (ECG) and echocardiograph (Echo) Doppler recordings. We examined 2248 single-nucleotide polymorphisms (SNPs) on chromosome 9p21 for association using a gene-centric statistical test. We replicated the aforementioned QTL [logarithm of odds (LOD) = 4.83; genome-wide P = 0.0003] on chromosome 9p21 in one SHFS population using joint linkage of ECG and Echo HR. After correcting for effective number of SNPs using a gene-centric test, six SNPs (rs7875153, rs7848524, rs4446809, rs10964759, rs1125488 and rs7853123) remained significant. We applied a novel bivariate association method, which was a joint test of association of a single locus to two traits using a standard additive genetic model. The SNP, rs7875153, provided the strongest evidence for association (P = 7.14 × 10-6). This SNP (rs7875153) is rare (minor allele frequency = 0.02) in AIs and is located within intron 9 of the gene KIAA1797. To support this association, we applied lymphocyte RNA expression data from the San Antonio Family Heart Study, a longitudinal study of CVD in Mexican Americans. Expression levels of KIAA1797 were significantly associated (P = 0.012) with HR. These findings in independent populations support that KIAA1797 genetic variation may be associated with HR but elucidation of a functional relationship requires additional study.

Original languageEnglish (US)
Article numberddq274
Pages (from-to)3662-3671
Number of pages10
JournalHuman Molecular Genetics
Volume19
Issue number18
DOIs
StatePublished - Jul 3 2010

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North American Indians
Heart Rate
Single Nucleotide Polymorphism
Chromosomes
Quantitative Trait Loci
Electrocardiography
Cardiovascular Diseases
Joints
Genes
Genetic Models
Gene Frequency
Introns
Population
Longitudinal Studies
Genome
Lymphocytes
RNA
Phenotype
Research

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Melton, P. E., Siegel, S. R., Voruganti, V. S., Göring, H. H. H., Laston, S., Haack, K., ... Almasy, L. (2010). Bivariate genetic association of KIAA1797 with heart rate in American Indians: The Strong Heart Family Study. Human Molecular Genetics, 19(18), 3662-3671. [ddq274]. https://doi.org/10.1093/hmg/ddq274
Melton, Phillip E. ; Siegel, Susan Rutherford ; Voruganti, Venkata Saroja ; Göring, Harald H.H. ; Laston, Sandra ; Haack, Karin ; Comuzzie, Anthony G. ; Dyer, Thomas D. ; Johnson, Matthew P. ; Kent, Jack W. ; Curran, Joanne E. ; Moses, Eric K. ; Blangero, John ; Barac, Ana ; Lee, Elisa T. ; Best, Lyle G. ; Fabsitz, Richard R. ; Devereux, Richard B. ; Okin, Peter M. ; Bella, Jonathan N. ; Broeckel, Uli ; Howard, Barbara V. ; MacCluer, Jean W. ; Cole, Shelley A. ; Almasy, Laura. / Bivariate genetic association of KIAA1797 with heart rate in American Indians : The Strong Heart Family Study. In: Human Molecular Genetics. 2010 ; Vol. 19, No. 18. pp. 3662-3671.
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abstract = "Heart rate (HR) has been identified as a risk factor for cardiovascular disease (CVD), yet little is known regarding genetic factors influencing this phenotype. Previous research in American Indians (AIs) from the Strong Heart Family Study (SHFS) identified a significant quantitative trait locus (QTL) for HR on chromosome 9p21. Genetic association on HR was conducted in the SHFS. HR was measured from electrocardiogram (ECG) and echocardiograph (Echo) Doppler recordings. We examined 2248 single-nucleotide polymorphisms (SNPs) on chromosome 9p21 for association using a gene-centric statistical test. We replicated the aforementioned QTL [logarithm of odds (LOD) = 4.83; genome-wide P = 0.0003] on chromosome 9p21 in one SHFS population using joint linkage of ECG and Echo HR. After correcting for effective number of SNPs using a gene-centric test, six SNPs (rs7875153, rs7848524, rs4446809, rs10964759, rs1125488 and rs7853123) remained significant. We applied a novel bivariate association method, which was a joint test of association of a single locus to two traits using a standard additive genetic model. The SNP, rs7875153, provided the strongest evidence for association (P = 7.14 × 10-6). This SNP (rs7875153) is rare (minor allele frequency = 0.02) in AIs and is located within intron 9 of the gene KIAA1797. To support this association, we applied lymphocyte RNA expression data from the San Antonio Family Heart Study, a longitudinal study of CVD in Mexican Americans. Expression levels of KIAA1797 were significantly associated (P = 0.012) with HR. These findings in independent populations support that KIAA1797 genetic variation may be associated with HR but elucidation of a functional relationship requires additional study.",
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Melton, PE, Siegel, SR, Voruganti, VS, Göring, HHH, Laston, S, Haack, K, Comuzzie, AG, Dyer, TD, Johnson, MP, Kent, JW, Curran, JE, Moses, EK, Blangero, J, Barac, A, Lee, ET, Best, LG, Fabsitz, RR, Devereux, RB, Okin, PM, Bella, JN, Broeckel, U, Howard, BV, MacCluer, JW, Cole, SA & Almasy, L 2010, 'Bivariate genetic association of KIAA1797 with heart rate in American Indians: The Strong Heart Family Study', Human Molecular Genetics, vol. 19, no. 18, ddq274, pp. 3662-3671. https://doi.org/10.1093/hmg/ddq274

Bivariate genetic association of KIAA1797 with heart rate in American Indians : The Strong Heart Family Study. / Melton, Phillip E.; Siegel, Susan Rutherford; Voruganti, Venkata Saroja; Göring, Harald H.H.; Laston, Sandra; Haack, Karin; Comuzzie, Anthony G.; Dyer, Thomas D.; Johnson, Matthew P.; Kent, Jack W.; Curran, Joanne E.; Moses, Eric K.; Blangero, John; Barac, Ana; Lee, Elisa T.; Best, Lyle G.; Fabsitz, Richard R.; Devereux, Richard B.; Okin, Peter M.; Bella, Jonathan N.; Broeckel, Uli; Howard, Barbara V.; MacCluer, Jean W.; Cole, Shelley A.; Almasy, Laura.

In: Human Molecular Genetics, Vol. 19, No. 18, ddq274, 03.07.2010, p. 3662-3671.

Research output: Contribution to journalArticle

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T1 - Bivariate genetic association of KIAA1797 with heart rate in American Indians

T2 - The Strong Heart Family Study

AU - Melton, Phillip E.

AU - Siegel, Susan Rutherford

AU - Voruganti, Venkata Saroja

AU - Göring, Harald H.H.

AU - Laston, Sandra

AU - Haack, Karin

AU - Comuzzie, Anthony G.

AU - Dyer, Thomas D.

AU - Johnson, Matthew P.

AU - Kent, Jack W.

AU - Curran, Joanne E.

AU - Moses, Eric K.

AU - Blangero, John

AU - Barac, Ana

AU - Lee, Elisa T.

AU - Best, Lyle G.

AU - Fabsitz, Richard R.

AU - Devereux, Richard B.

AU - Okin, Peter M.

AU - Bella, Jonathan N.

AU - Broeckel, Uli

AU - Howard, Barbara V.

AU - MacCluer, Jean W.

AU - Cole, Shelley A.

AU - Almasy, Laura

PY - 2010/7/3

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Melton PE, Siegel SR, Voruganti VS, Göring HHH, Laston S, Haack K et al. Bivariate genetic association of KIAA1797 with heart rate in American Indians: The Strong Heart Family Study. Human Molecular Genetics. 2010 Jul 3;19(18):3662-3671. ddq274. https://doi.org/10.1093/hmg/ddq274