Faculty Collaboration Database

Bivariate genetic association of KIAA1797 with heart rate in American Indians: the Strong Heart Family Study. Hum Mol Genet 2010 Sep 15;19(18):3662-71

Date

07/06/2010

Pubmed ID

20601674

Pubmed Central ID

PMC2928129

DOI

10.1093/hmg/ddq274

Scopus ID

2-s2.0-77956102449 (requires institutional sign-in at Scopus site)   20 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 x 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 List

Melton PE, Rutherford S, Voruganti VS, Göring HH, Laston S, Haack K, Comuzzie AG, Dyer TD, Johnson MP, Kent JW Jr, 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

Author

Ulrich Broeckel MD Chief, Center Associate Director, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Cardiovascular Diseases
Electrocardiography
Family
Fanconi Anemia Complementation Group Proteins
Female
Genetic Predisposition to Disease
Heart Rate
Humans
Indians, North American
Male
Middle Aged
Pedigree
Polymorphism, Single Nucleotide
Risk Factors
Young Adult