Genetic analysis of hsCRP in American Indians: The Strong heart family study
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Best, L.G, et al. Genetic Analysis of Hscrp In American Indians: The Strong Heart Family Study. 2019. https://doi.org/10.17615/2b2y-1r36APA
Best, L., Balakrishnan, P., Cole, S., Haack, K., Kocarnik, J., Pankratz, N., Anderson, M., Franceschini, N., Howard, B., Lee, E., North, K., Umans, J., Yracheta, J., Navas Acien, A., & Voruganti, V. (2019). Genetic analysis of hsCRP in American Indians: The Strong heart family study. https://doi.org/10.17615/2b2y-1r36Chicago
Best, L.G., P Balakrishnan, S.A Cole, K Haack, J.M Kocarnik, N Pankratz, M.Z Anderson et al. 2019. Genetic Analysis of Hscrp In American Indians: The Strong Heart Family Study. https://doi.org/10.17615/2b2y-1r36- Creator
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Best, L.G.
- Other Affiliation: Missouri Breaks Industries Research Inc.
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Balakrishnan, P.
- Other Affiliation: University of Alabama at Birmingham
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Cole, S.A.
- Other Affiliation: Texas Biomedical Research Institute
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Haack, K.
- Other Affiliation: Texas Biomedical Research Institute
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Kocarnik, J.M.
- Other Affiliation: Fred Hutchinson Cancer Research Center
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Pankratz, N.
- Other Affiliation: University of Minnesota
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Anderson, M.Z.
- Other Affiliation: Ohio State University
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Franceschini, N.
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology
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Howard, B.V.
- Other Affiliation: MedStar Health Research Institute
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Lee, E.T.
- Other Affiliation: University of Oklahoma Health Sciences Center
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North, K.E.
- Affiliation: Gillings School of Global Public Health
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Umans, J.G.
- Other Affiliation: MedStar Health Research Institute
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Yracheta, J.M.
- Other Affiliation: Columbia University
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Navas-Acien, A.
- Other Affiliation: Columbia University
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Voruganti, V.S.
- Affiliation: Gillings School of Global Public Health, Department of Nutrition
- Abstract
- Background 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. Methods 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. Results 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. Conclusion 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.
- Date of publication
- 2019
- Keyword
- hepatocyte nuclear factor 1alpha
- human
- population genetics
- C-Reactive Protein
- adult
- genetic linkage
- genetics
- Genetic Variation
- Humans
- genetic variability
- Biomarkers
- chromosome 2
- chromosome 5
- Genome-Wide Association Study
- male
- single nucleotide polymorphism
- biological marker
- chromosome 9
- microsatellite marker
- American Indian
- genetic variation
- Indians, North American
- Genetics, Population
- Female
- Alleles
- heritability
- blood
- Polymorphism, Single Nucleotide
- gene locus
- Article
- chromosome 6
- Genetic Linkage
- protein blood level
- Genetic Predisposition to Disease
- Male
- allele
- major clinical study
- genotype
- genome-wide association study
- genetic predisposition
- chromosome 10
- female
- cohort analysis
- chromosome 17
- Genotype
- CRP gene
- C reactive protein
- HNF1A gene
- genetic association
- DOI
- Identifier
- Resource type
- Article
- License
- Attribution 4.0 International
- Journal title
- PLoS ONE
- Journal volume
- 14
- Journal issue
- 10
- Language
- English
- Version
- Publisher
- Funder
- National Institutes of Health, NIH
- National Heart, Lung, and Blood Institute, NHLBI: HL109301
- National Institute of Environmental Health Sciences, NIEHS: ES021367
- National Institute of Diabetes and Digestive and Kidney Diseases, NIDDK: DK092238, HL109284, HL109315, HL109319, P30DK056350
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