title: Fasting glucose GWAS candidate region analysis across ethnic groups in the Multiethnic Study of Atherosclerosis (MESA).
abstract: Genetic variants associated with fasting glucose in European ancestry populations are increasingly well understood. However, the nature of the associations between these single nucleotide polymorphisms (SNPs) and fasting glucose in other racial and ethnic groups is unclear. We sought to examine regions previously identified to be associated with fasting glucose in Caucasian genome-wide association studies (GWAS) across multiple ethnicities in the Multiethnic Study of Atherosclerosis (MESA). Nondiabetic MESA participants with fasting glucose measured at the baseline exam and with GWAS genotyping were included; 2,349 Caucasians, 664 individuals of Chinese descent, 1,366 African Americans, and 1,171 Hispanics. Genotype data were generated from the Affymetrix 6.0 array and imputation in IMPUTE. Fasting glucose was regressed on SNP dosage data in each ethnic group adjusting for age, gender, MESA study center, and ethnic-specific principal components. SNPs from the three gene regions with the strongest associations to fasting glucose in previous Caucasian GWAS (MTNR1B / GCK / G6PC2) were examined in depth. There was limited power to replicate associations in other ethnic groups due to smaller allele frequencies and limited sample size; SNP associations may also have differed across ethnic groups due to differing linkage disequilibrium patterns with causal variants. rs10830963 in MTNR1B and rs4607517 in GCK demonstrated consistent magnitude and direction of association with fasting glucose across ethnic groups, although the associations were often not nominally significant. In conclusion, certain SNPs in MTNR1B and GCK demonstrate consistent effects across four racial and ethnic groups, narrowing the putative region for these causal variants.
authors.affiliation: Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA. ljrtorvik@northwestern.edu
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Rasmussen-Torvik
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Guo
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
authors.forename: Alain G
authors.initials: AG
authors.lastname: Bertoni
authors.forename: Michele M
authors.initials: MM
authors.lastname: Sale
authors.forename: Jie
authors.initials: J
authors.lastname: Yao
authors.forename: David A
authors.initials: DA
authors.lastname: Bluemke
authors.forename: Mark O
authors.initials: MO
authors.lastname: Goodarzi
authors.forename: Y Ida
authors.initials: YI
authors.lastname: Chen
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Vaidya
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Raffel
authors.forename: George J
authors.initials: GJ
authors.lastname: Papanicolaou
authors.forename: James B
authors.initials: JB
authors.lastname: Meigs
authors.forename: James S
authors.initials: JS
authors.lastname: Pankow
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D050197:Atherosclerosis / Q000208:ethnology* / Q000235:genetics*; D001786:Blood Glucose / Q000032:analysis; D005006:Ethnicity; D005215:Fasting; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012044:Regression Analysis
chemical_list: D001786:Blood Glucose