1. Discovery, fine-mapping, and conditional analyses of genetic variants associated with C-reactive protein in multiethnic populations using the Metabochip in the Population Architecture using Genomics and Epidemiology (PAGE) study
- Author
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Kocarnik, Jonathan M, Richard, Melissa, Graff, Misa, Haessler, Jeffrey, Bien, Stephanie, Carlson, Chris, Carty, Cara L, Reiner, Alexander P, Avery, Christy L, Ballantyne, Christie M, LaCroix, Andrea Z, Assimes, Themistocles L, Barbalic, Maja, Pankratz, Nathan, Tang, Weihong, Tao, Ran, Chen, Dongquan, Talavera, Gregory A, Daviglus, Martha L, Chirinos-Medina, Diana A, Pereira, Rocio, Nishimura, Katie, Bůžková, Petra, Best, Lyle G, Ambite, José Luis, Cheng, Iona, Crawford, Dana C, Hindorff, Lucia A, Fornage, Myriam, Heiss, Gerardo, North, Kari E, Haiman, Christopher A, Peters, Ulrike, Le Marchand, Loic, and Kooperberg, Charles
- Subjects
Genetics ,Clinical Research ,Human Genome ,2.1 Biological and endogenous factors ,Aetiology ,C-Reactive Protein ,Carbon-Carbon Lyases ,Enoyl-CoA Hydratase ,Female ,Genome-Wide Association Study ,Glycoproteins ,Group VI Phospholipases A2 ,Humans ,Linkage Disequilibrium ,Male ,Metagenomics ,Molecular Epidemiology ,Polymorphism ,Single Nucleotide ,Whites ,White People ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
C-reactive protein (CRP) is a circulating biomarker indicative of systemic inflammation. We aimed to evaluate genetic associations with CRP levels among non-European-ancestry populations through discovery, fine-mapping and conditional analyses. A total of 30 503 non-European-ancestry participants from 6 studies participating in the Population Architecture using Genomics and Epidemiology study had serum high-sensitivity CRP measurements and ∼200 000 single nucleotide polymorphisms (SNPs) genotyped on the Metabochip. We evaluated the association between each SNP and log-transformed CRP levels using multivariate linear regression, with additive genetic models adjusted for age, sex, the first four principal components of genetic ancestry, and study-specific factors. Differential linkage disequilibrium patterns between race/ethnicity groups were used to fine-map regions associated with CRP levels. Conditional analyses evaluated for multiple independent signals within genetic regions. One hundred and sixty-three unique variants in 12 loci in overall or race/ethnicity-stratified Metabochip-wide scans reached a Bonferroni-corrected P-value
- Published
- 2018