title: Multiancestral analysis of inflammation-related genetic variants and C-reactive protein in the population architecture using genomics and epidemiology study.
abstract: BACKGROUND
  C-reactive protein (CRP) is a biomarker of inflammation. Genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) associated with CRP concentrations and inflammation-related traits such as cardiovascular disease, type 2 diabetes mellitus, and obesity. We aimed to replicate previous CRP-SNP associations, assess whether these associations generalize to additional race/ethnicity groups, and evaluate inflammation-related SNPs for a potentially pleiotropic association with CRP.
  
  
  RESULTS
  We selected and analyzed 16 CRP-associated and 250 inflammation-related GWAS SNPs among 40 473 African American, American Indian, Asian/Pacific Islander, European American, and Hispanic participants from 7 studies collaborating in the Population Architecture using Genomics and Epidemiology (PAGE) study. Fixed-effect meta-analyses combined study-specific race/ethnicity-stratified linear regression estimates to evaluate the association between each SNP and high-sensitivity CRP. Overall, 18 SNPs in 8 loci were significantly associated with CRP (Bonferroni-corrected P<3.1×10(-3) for replication, P<2.0×10(-4) for pleiotropy): Seven of these were specific to European Americans, while 9 additionally generalized to African Americans (1), Hispanics (5), or both (3); 1 SNP was seen only in African Americans and Hispanics. Two SNPs in the CELSR2/PSRC1/SORT1 locus showed a potentially novel association with CRP: rs599839 (P=2.0×10(-6)) and rs646776 (P=3.1×10(-5)).
  
  
  CONCLUSIONS
  We replicated 16 SNP-CRP associations, 10 of which generalized to African Americans and/or Hispanics. We also identified potentially novel pleiotropic associations with CRP for two SNPs previously associated with coronary artery disease and/or low-density lipoprotein-cholesterol. These findings demonstrate the benefit of evaluating genotype-phenotype associations in multiple race/ethnicity groups and looking for pleiotropic relationships among SNPs previously associated with related phenotypes.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Kocarnik
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Pendergrass
authors.forename: Cara L
authors.initials: CL
authors.lastname: Carty
authors.forename: James S
authors.initials: JS
authors.lastname: Pankow
authors.forename: Fredrick R
authors.initials: FR
authors.lastname: Schumacher
authors.forename: Iona
authors.initials: I
authors.lastname: Cheng
authors.forename: Peter
authors.initials: P
authors.lastname: Durda
authors.forename: José Luis
authors.initials: JL
authors.lastname: Ambite
authors.forename: Ewa
authors.initials: E
authors.lastname: Deelman
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Cook
authors.forename: Simin
authors.initials: S
authors.lastname: Liu
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
authors.forename: Carolyn
authors.initials: C
authors.lastname: Hutter
authors.forename: Kristin
authors.initials: K
authors.lastname: Brown-Gentry
authors.forename: Sarah
authors.initials: S
authors.lastname: Wilson
authors.forename: Lyle G
authors.initials: LG
authors.lastname: Best
authors.forename: Nathan
authors.initials: N
authors.lastname: Pankratz
authors.forename: Ching-Ping
authors.initials: CP
authors.lastname: Hong
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Cole
authors.forename: V Saroja
authors.initials: VS
authors.lastname: Voruganti
authors.forename: Petra
authors.initials: P
authors.lastname: Bůžkova
authors.forename: Neal W
authors.initials: NW
authors.lastname: Jorgensen
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Jenny
authors.forename: Lynne R
authors.initials: LR
authors.lastname: Wilkens
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
authors.forename: Andrea
authors.initials: A
authors.lastname: Lacroix
authors.forename: Kari
authors.initials: K
authors.lastname: North
authors.forename: Rebecca
authors.initials: R
authors.lastname: Jackson
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Lucia A
authors.initials: LA
authors.lastname: Hindorff
authors.forename: Dana C
authors.initials: DC
authors.lastname: Crawford
authors.forename: Myron
authors.initials: M
authors.lastname: Gross
authors.forename: Ulrike
authors.initials: U
authors.lastname: Peters
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D002097:C-Reactive Protein / Q000378:metabolism*; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D007249:Inflammation / Q000097:blood / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014481:United States / Q000453:epidemiology; D055815:Young Adult; D001741:Black or African American
chemical_list: D002097:C-Reactive Protein
keywords: C-reactive protein; continental population groups; ethnic groups; genetic pleiotropy; inflammation; molecular epidemiology; polymorphism, single nucleotide