@article {6633, title = {Consistent directions of effect for established type 2 diabetes risk variants across populations: the population architecture using Genomics and Epidemiology (PAGE) Consortium.}, journal = {Diabetes}, volume = {61}, year = {2012}, month = {2012 Jun}, pages = {1642-7}, abstract = {

Common genetic risk variants for type 2 diabetes (T2D) have primarily been identified in populations of European and Asian ancestry. We tested whether the direction of association with 20 T2D risk variants generalizes across six major racial/ethnic groups in the U.S. as part of the Population Architecture using Genomics and Epidemiology Consortium (16,235 diabetes case and 46,122 control subjects of European American, African American, Hispanic, East Asian, American Indian, and Native Hawaiian ancestry). The percentage of positive (odds ratio [OR] >1 for putative risk allele) associations ranged from 69\% in American Indians to 100\% in European Americans. Of the nine variants where we observed significant heterogeneity of effect by racial/ethnic group (P(heterogeneity) < 0.05), eight were positively associated with risk (OR >1) in at least five groups. The marked directional consistency of association observed for most genetic variants across populations implies a shared functional common variant in each region. Fine-mapping of all loci will be required to reveal markers of risk that are important within and across populations.

}, keywords = {Adult, Aged, Aged, 80 and over, Alleles, Diabetes Mellitus, Type 2, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Metagenomics, Middle Aged, Population Groups, Risk, Risk Factors}, issn = {1939-327X}, doi = {10.2337/db11-1296}, author = {Haiman, Christopher A and Fesinmeyer, Megan D and Spencer, Kylee L and B{\r u}zkov{\'a}, Petra and Voruganti, V Saroja and Wan, Peggy and Haessler, Jeff and Franceschini, Nora and Monroe, Kristine R and Howard, Barbara V and Jackson, Rebecca D and Florez, Jose C and Kolonel, Laurence N and Buyske, Steven and Goodloe, Robert J and Liu, Simin and Manson, JoAnn E and Meigs, James B and Waters, Kevin and Mukamal, Kenneth J and Pendergrass, Sarah A and Shrader, Peter and Wilkens, Lynne R and Hindorff, Lucia A and Ambite, Jose Luis and North, Kari E and Peters, Ulrike and Crawford, Dana C and Le Marchand, Lo{\"\i}c and Pankow, James S} } @article {6360, title = {Multiancestral analysis of inflammation-related genetic variants and C-reactive protein in the population architecture using genomics and epidemiology study.}, journal = {Circ Cardiovasc Genet}, volume = {7}, year = {2014}, month = {2014 Apr}, pages = {178-88}, 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.

METHODS AND 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{\texttimes}10(-3) for replication, P<2.0{\texttimes}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{\texttimes}10(-6)) and rs646776 (P=3.1{\texttimes}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.

}, keywords = {Adult, African Continental Ancestry Group, Aged, Asian Continental Ancestry Group, C-Reactive Protein, Female, Genetic Variation, Genome-Wide Association Study, Hispanic Americans, Humans, Indians, North American, Inflammation, Male, Middle Aged, Polymorphism, Single Nucleotide, United States, Young Adult}, issn = {1942-3268}, doi = {10.1161/CIRCGENETICS.113.000173}, author = {Kocarnik, Jonathan M and Pendergrass, Sarah A and Carty, Cara L and Pankow, James S and Schumacher, Fredrick R and Cheng, Iona and Durda, Peter and Ambite, Jose Luis and Deelman, Ewa and Cook, Nancy R and Liu, Simin and Wactawski-Wende, Jean and Hutter, Carolyn and Brown-Gentry, Kristin and Wilson, Sarah and Best, Lyle G and Pankratz, Nathan and Hong, Ching-Ping and Cole, Shelley A and Voruganti, V Saroja and B{\r u}zkov{\'a}, Petra and Jorgensen, Neal W and Jenny, Nancy S and Wilkens, Lynne R and Haiman, Christopher A and Kolonel, Laurence N and LaCroix, Andrea and North, Kari and Jackson, Rebecca and Le Marchand, Lo{\"\i}c and Hindorff, Lucia A and Crawford, Dana C and Gross, Myron and Peters, Ulrike} }