Genetic analysis of hsCRP in American Indians: The Strong Heart Family Study

Increased serum levels of C-reactive protein (CRP), an important component of the innate immune response, are associated with increased risk of cardiovascular disease (CVD). Multiple single nucleotide polymorphisms (SNP) have been identified which are associated with CRP levels, and Mendelian random...

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Published in:PloS one Vol. 14; no. 10; p. e0223574
Main Authors: Best, Lyle G., Balakrishnan, Poojitha, Cole, Shelley A., Haack, Karin, Kocarnik, Jonathan M., Pankratz, Nathan, Anderson, Matthew Z., Franceschini, Nora, Howard, Barbara V., Lee, Elisa T., North, Kari E., Umans, Jason G., Yracheta, Joseph M., Navas-Acien, Ana, Voruganti, V. Saroja
Format: Journal Article
Language:English
Published: United States Public Library of Science 17.10.2019
Public Library of Science (PLoS)
Subjects:
African Americans
Alleles
Biology and Life Sciences
Biomarkers - blood
Biomedical research
C-reactive protein
C-Reactive Protein - genetics
Cancer
Cardiovascular diseases
Chromosomes
Colon
Colon cancer
Colorectal cancer
Diabetes
Environmental health
Family studies
Female
Gene loci
Genetic analysis
Genetic diversity
Genetic Linkage
Genetic markers
Genetic Predisposition to Disease
Genetic variance
Genetic Variation
Genetics, Population
Genome-Wide Association Study
Genomes
Genomics
Genotype
Genotypes
Health risks
Health sciences
Heart diseases
Heritability
Humans
Immune response
Indians, North American - genetics
Influence
Innate immunity
Male
Markers
Medical research
Medicine and Health Sciences
Metabolism
Microsatellites
Minority & ethnic groups
Native Americans
Nucleotides
Nutrition research
Obesity
Polymorphism, Single Nucleotide
Population genetics
Populations
Proteins
Public health
Serum levels
Single-nucleotide polymorphism
Studies
New York
Ohio
United States > US
Texas
Missouri
ISSN:1932-6203, 1932-6203
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Summary:Increased serum levels of C-reactive protein (CRP), an important component of the innate immune response, are associated with increased risk of cardiovascular disease (CVD). Multiple single nucleotide polymorphisms (SNP) have been identified which are associated with CRP levels, and Mendelian randomization studies have shown a positive association between SNPs increasing CRP expression and risk of colon cancer (but thus far not CVD). The effects of individual genetic variants often interact with the genetic background of a population and hence we sought to resolve the genetic determinants of serum CRP in a number of American Indian populations. The Strong Heart Family Study (SHFS) has serum CRP measurements from 2428 tribal members, recruited as large families from three regions of the United States. Microsatellite markers and MetaboChip defined SNP genotypes were incorporated into variance components, decomposition-based linkage and association analyses. CRP levels exhibited significant heritability (h2 = 0.33 ± 0.05, p<1.3 X 10-20). A locus on chromosome (chr) 6, near marker D6S281 (approximately at 169.6 Mb, GRCh38/hg38) showed suggestive linkage (LOD = 1.9) to CRP levels. No individual SNPs were found associated with CRP levels after Bonferroni adjustment for multiple testing (threshold <7.77 x 10-7), however, we found nominal associations, many of which replicate previous findings at the CRP, HNF1A and 7 other loci. In addition, we report association of 46 SNPs located at 7 novel loci on chromosomes 2, 5, 6(2 loci), 9, 10 and 17, with an average of 15.3 Kb between SNPs and all with p-values less than 7.2 X 10-4. In agreement with evidence from other populations, these data show CRP serum levels are under considerable genetic influence; and include loci, such as near CRP and other genes, that replicate results from other ethnic groups. These findings also suggest possible novel loci on chr 6 and other chromosomes that warrant further investigation.
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Competing Interests: MBIRI does not alter our adherence to PLOS ONE policies on sharing data and materials.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0223574