Bivariate genetic association of KIAA1797 with heart rate in American Indians: The Strong Heart Family Study
Melton, PE and Rutherford, S and Voruganti, VS and Goring, HH and Laston, S and Haack, K and Comuzzie, AG and Dyer, TD and Johnson, MP and Kent Jr, JW and Curran, JE and Moses, EK and Blangero, J and Barac, A and Lee, ET and Best, LG and Fabsitz, RR and Devereux, RB and Okin, PM and Bella, JN and Broeckel, U and Howard, BV and MacCluer, JW and Cole, SA and Almasy, L, Bivariate genetic association of KIAA1797 with heart rate in American Indians: The Strong Heart Family Study, Human Molecular Genetics, 19, (18) pp. 3662-3671. ISSN 0964-6906 (2010) [Refereed Article]
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) 5 4.83; genome-wide P 5 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 5 7.14 3 1026
). This SNP (rs7875153) is rare (minor allele frequency 5 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 5 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.
American Indians, family study, focal adhesion, heart rate, family studies