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

Phillip E. Melton; Sue Rutherford; 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. Bella; Uli Broeckel; Barbara V. Howard; Jean W. MacCluer; Shelley A. Cole; Laura Almasy

doi:10.1093/hmg/ddq274

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

Phillip E. Melton, Sue Rutherford, 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

Biobehavioral Health

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

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 language	English (US)
Article number	ddq274
Pages (from-to)	3662-3671
Number of pages	10
Journal	Human molecular genetics
Volume	19
Issue number	18
DOIs	https://doi.org/10.1093/hmg/ddq274
State	Published - Jul 3 2010

All Science Journal Classification (ASJC) codes

Molecular Biology
Genetics
Genetics(clinical)

Access to Document

10.1093/hmg/ddq274

Cite this

Melton, P. E., Rutherford, S., Voruganti, V. S., Göring, H. H. H., Laston, S., Haack, K., Comuzzie, A. G., Dyer, T. D., Johnson, M. P., Kent, J. W., Curran, J. E., Moses, E. K., Blangero, J., Barac, A., Lee, E. T., Best, L. G., Fabsitz, R. R., Devereux, R. B., Okin, P. M., ... 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. Article ddq274. https://doi.org/10.1093/hmg/ddq274

@article{a59782b4a8734bc49801758746aaa8a1,

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

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.",

author = "Melton, {Phillip E.} and Sue Rutherford and Voruganti, {Venkata Saroja} and G{\"o}ring, {Harald H.H.} and Sandra Laston and Karin Haack and Comuzzie, {Anthony G.} and Dyer, {Thomas D.} and Johnson, {Matthew P.} and Kent, {Jack W.} and Curran, {Joanne E.} and Moses, {Eric K.} and John Blangero and Ana Barac and Lee, {Elisa T.} and Best, {Lyle G.} and Fabsitz, {Richard R.} and Devereux, {Richard B.} and Okin, {Peter M.} and Bella, {Jonathan N.} and Uli Broeckel and Howard, {Barbara V.} and MacCluer, {Jean W.} and Cole, {Shelley A.} and Laura Almasy",

year = "2010",

month = jul,

day = "3",

doi = "10.1093/hmg/ddq274",

language = "English (US)",

volume = "19",

pages = "3662--3671",

journal = "Human molecular genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "18",

}

Melton, PE, Rutherford, S, 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

TY - JOUR

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

T2 - The Strong Heart Family Study

AU - Melton, Phillip E.

AU - Rutherford, Sue

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

Y1 - 2010/7/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77956102449&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956102449&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddq274

DO - 10.1093/hmg/ddq274

M3 - Article

C2 - 20601674

AN - SCOPUS:77956102449

SN - 0964-6906

VL - 19

SP - 3662

EP - 3671

JO - Human molecular genetics

JF - Human molecular genetics

IS - 18

M1 - ddq274

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this