NDLI: Fine-mapping the genetic basis of CRP regulation in African Americans: a Bayesian approach

Content Provider	Springer Nature Link
Author	Rhodes, Benjamin Morris, David L. Subrahmanyan, Lakshman Aubin, Cristin Leon, Carlos F. Mendes Kelly, Jeremiah F. Evans, Dennis A. Whittaker, John C. Oksenberg, Jorge R. Jager, Philip L. Vyse, Tim J.
Copyright Year	2008
Abstract	Basal levels of C-reactive protein (CRP) have been associated with disease, particularly future cardiovascular events. Twin studies estimate 50% CRP heritability, so the identification of genetic variants influencing CRP expression is important. Existing studies in populations of European ancestry have identified numerous cis-acting variants but leave significant ambiguity over the identity of the key functional polymorphisms. We addressed this issue by typing a dense map of CRP single-nucleotide polymorphisms (SNPs), and quantifying serum CRP in 594 unrelated African Americans. We used Bayesian model choice analysis to select the combination of SNPs best explaining basal CRP and found strong support for triallelic rs3091244 alone, with the T allele acting in an additive manner (Bayes factor > 100 vs. null model), with additional support for a model incorporating both rs3091244 and rs12728740. Admixture analysis suggested SNP rs12728740 segregated with haplotypes predicted to be of recent European origin. Using a cladistic approach we confirmed the importance of rs3091244(T) by demonstrating a significant partition of haplotype effect based on the rs3091244(C/T) mutation (F = 8.91, P = 0.006). We argue that weaker linkage disequilibrium across the African American CRP locus compared with Europeans has allowed us to establish an unambiguous functional role for rs3091244(T), while also recognising the potential for additional functional mutations present in the European genome.
Starting Page	633
Ending Page	642
Page Count	10
File Format	PDF
ISSN	03406717
Journal	Human Genetics
Volume Number	123
Issue Number	6
e-ISSN	14321203
Language	English
Publisher	Springer-Verlag
Publisher Date	2008-05-24
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Metabolic Diseases Gene Function Molecular Medicine Human Genetics
Content Type	Text
Resource Type	Article
Subject	Genetics Genetics (clinical)

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