title: Trans-ethnic fine mapping identifies a novel independent locus at the 3' end of CDKAL1 and novel variants of several susceptibility loci for type 2 diabetes in a Han Chinese population.
abstract: OBJECTIVE
  Candidate gene and genome-wide association studies have identified ∼60 susceptibility loci for type 2 diabetes. A majority of these loci have been discovered and tested only in European populations. The aim of this study was to assess the presence and extent of trans-ethnic effects of these loci in an East Asian population.
  
  
  METHODS
  A total of 9,335 unrelated Chinese Han individuals, including 4,535 with type 2 diabetes and 4,800 non-diabetic ethnically matched controls, were genotyped using the Illumina 200K Metabochip. We tested 50 established loci for type 2 diabetes and related traits (fasting glucose, fasting insulin, 2 h glucose). Disease association with the additive model of inheritance was analysed with logistic regression.
  
  
  RESULTS
  We found that 14 loci significantly transferred to the Chinese population, with two loci (p = 5.7 × 10(-12) for KCNQ1; p = 5.0 × 10(-8) for CDKN2A/B-CDKN2BAS) reaching independent genome-wide statistical significance. Five of these 14 loci had similar lead single-nucleotide polymorphisms (SNPs) as were found in the European studies while the other nine were different. Further stepwise conditional analysis identified a total of seven secondary signals and an independent novel locus at the 3' end of CDKAL1.
  
  
  CONCLUSIONS
  These results suggest that many loci associated with type 2 diabetes are commonly shared between European and Chinese populations. Identification of population-specific SNPs may increase our understanding of the genetic architecture underlying type 2 diabetes in different ethnic populations.
authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute, Harbor-UCLA Medical Center, 1124 W. Carson Street, Torrance, CA, 90502, USA.
authors.forename: Jane Z
authors.initials: JZ
authors.lastname: Kuo
authors.forename: Wayne Huey-Herng
authors.initials: WH
authors.lastname: Sheu
authors.forename: Themistocles L
authors.initials: TL
authors.lastname: Assimes
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Hung
authors.forename: Devin
authors.initials: D
authors.lastname: Absher
authors.forename: Yen-Feng
authors.initials: YF
authors.lastname: Chiu
authors.forename: Jordan
authors.initials: J
authors.lastname: Mak
authors.forename: Jun-Sing
authors.initials: JS
authors.lastname: Wang
authors.forename: Soonil
authors.initials: S
authors.lastname: Kwon
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Hsu
authors.forename: Mark O
authors.initials: MO
authors.lastname: Goodarzi
authors.forename: I-Te
authors.initials: IT
authors.lastname: Lee
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Knowles
authors.forename: Brittany E
authors.initials: BE
authors.lastname: Miller
authors.forename: Wen-Jane
authors.initials: WJ
authors.lastname: Lee
authors.forename: Jyh-Ming J
authors.initials: JM
authors.lastname: Juang
authors.forename: Tzung-Dau
authors.initials: TD
authors.lastname: Wang
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Guo
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
authors.forename: Lee-Ming
authors.initials: LM
authors.lastname: Chuang
authors.forename: Chao A
authors.initials: CA
authors.lastname: Hsiung
authors.forename: Thomas
authors.initials: T
authors.lastname: Quertermous
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Yii-Der I
authors.initials: YD
authors.lastname: Chen
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics*; D001786:Blood Glucose / Q000378:metabolism; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics*; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*; D012359:tRNA Methyltransferases
chemical_list: D001786:Blood Glucose; D007328:Insulin; D012359:tRNA Methyltransferases; D051360:Cyclin-Dependent Kinase 5; C525110:CDKAL1 protein, human