title: Replication of genome-wide association signals in Asian Indians with early-onset type 2 diabetes.
abstract: OBJECTIVE
  To evaluate the association of 87 genetic variants previously associated with type 2 diabetes mellitus (T2DM) in genome-wide association studies of populations of European ancestry in an Asian Indian population with early-onset type 2 diabetes mellitus (EOT2DM).
  
  
  METHODS
  The study groups comprised of 877 type 2 diabetes individuals, 436 individuals with EOT2DM (age at diagnosis below 35 years), 441 individuals with older T2DM (diagnosis at 35 years or greater) and controls with normal glucose tolerance (NGT) (n = 400 younger than 35 years; n = 438 older than 35 years). The participants were genotyped for 87 SNPs from 44 genes and 27 intergenic loci. Associations were tested using logistic regression.
  
  
  RESULTS
  All the variants in TCF7L2 and CDKN2A/2B showed study-wide significance (p < 1.4 × 10-4) with T2DM, but only rs7903146, rs12243326, rs12255372 of TCF7L2 and rs7020996 of CDKN2A/2B showed study-wide significance (p < 1.4 × 10-4) with EOT2DM in this population. In addition, an intergenic SNP on chromosome 1 (rs10493685) was also shown to be study-wide significant (p = 7.1 × 10-6). Several additional SNPs previously associated with T2DM reached borderline significance in this study, but may have been limited by relatively low sample numbers. Various other SNPs of T2DM were not associated with EOT2DM.
  
  
  CONCLUSIONS
  Some of the variants in TCF7L2 and CDKN2A/2B associated with T2DM are associated with EOT2DM as well. An intergenic SNP on chromosome 1p31 showed association only with early-onset T2DM in this Asian Indian population. The lack of association with many other SNPs of T2DM may be a reflection of the lack of power of the study, sample size, differences in the frequencies of genetic polymorphisms in different ethnic groups, effect sizes, as well as ancestral differences in pattern of LD between the genetic variants involved in early- and late-onset T2DM.
authors.affiliation: Madras Diabetes Research Foundation, 4, Conran Smith Road, Gopalapuram, Chennai, 600 086, India.|Division of Cardiovascular Research, Sidra Medical and Research Center, Doha, Qatar.
authors.forename: Manickam
authors.initials: M
authors.lastname: Chidambaram
authors.affiliation: Madras Diabetes Research Foundation, 4, Conran Smith Road, Gopalapuram, Chennai, 600 086, India.
authors.forename: Samuel
authors.initials: S
authors.lastname: Liju
authors.affiliation: Diabetologist and Endocrine and Metabolic Physician at Diabetes Care and Hormone Clinic, Ahmedabad, Gujarat, India.
authors.forename: Banshi
authors.initials: B
authors.lastname: Saboo
authors.affiliation: M.V. Hospital for Diabetes and Prof. M. Viswanathan Diabetes Research Centre, Chennai, Tamil Nadu, India.
authors.forename: Kumpatla
authors.initials: K
authors.lastname: Sathyavani
authors.affiliation: M.V. Hospital for Diabetes and Prof. M. Viswanathan Diabetes Research Centre, Chennai, Tamil Nadu, India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Viswanathan
authors.affiliation: Department of Laboratory Medicine Pathology, Medical School University of Minnesota, Minneapolis, MN, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Pankratz
authors.affiliation: Department of Laboratory Medicine Pathology, Medical School University of Minnesota, Minneapolis, MN, USA.
authors.forename: Myron
authors.initials: M
authors.lastname: Gross
authors.affiliation: Madras Diabetes Research Foundation, 4, Conran Smith Road, Gopalapuram, Chennai, 600 086, India.|Dr. Mohan's Diabetes Specialities Centre, WHO Collaborating Centre for Non-Communicable Diseases Prevention and Control, IDF Centre of Education, Chennai, India.
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Mohan
authors.affiliation: Madras Diabetes Research Foundation, 4, Conran Smith Road, Gopalapuram, Chennai, 600 086, India. radharv@yahoo.co.in.
authors.forename: Venkatesan
authors.initials: V
authors.lastname: Radha
mesh_terms: D000328:Adult; D017668:Age of Onset; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D005006:Ethnicity; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D005951:Glucose Tolerance Test / Q000379:methods; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
keywords: Asian Indian population; Early onset T2D; GWAS replication