title: Amerind ancestry, socioeconomic status and the genetics of type 2 diabetes in a Colombian population.
abstract: The "thrifty genotype" hypothesis proposes that the high prevalence of type 2 diabetes (T2D) in Native Americans and admixed Latin Americans has a genetic basis and reflects an evolutionary adaptation to a past low calorie/high exercise lifestyle. However, identification of the gene variants underpinning this hypothesis remains elusive. Here we assessed the role of Native American ancestry, socioeconomic status (SES) and 21 candidate gene loci in susceptibility to T2D in a sample of 876 T2D cases and 399 controls from Antioquia (Colombia). Although mean Native American ancestry is significantly higher in T2D cases than in controls (32% v 29%), this difference is confounded by the correlation of ancestry with SES, which is a stronger predictor of disease status. Nominally significant association (P<0.05) was observed for markers in: TCF7L2, RBMS1, CDKAL1, ZNF239, KCNQ1 and TCF1 and a significant bias (P<0.05) towards OR>1 was observed for markers selected from previous T2D genome-wide association studies, consistent with a role for Old World variants in susceptibility to T2D in Latin Americans. No association was found to the only known Native American-specific gene variant previously associated with T2D in a Mexican sample (rs9282541 in ABCA1). An admixture mapping scan with 1,536 ancestry informative markers (AIMs) did not identify genome regions with significant deviation of ancestry in Antioquia. Exclusion analysis indicates that this scan rules out ~95% of the genome as harboring loci with ancestry risk ratios >1.22 (at P < 0.05).
authors.affiliation: Department of Genetics, Evolution and Environment, University College London, London, United Kingdom.
authors.forename: Desmond D
authors.initials: DD
authors.lastname: Campbell
authors.forename: Maria V
authors.initials: MV
authors.lastname: Parra
authors.forename: Constanza
authors.initials: C
authors.lastname: Duque
authors.forename: Natalia
authors.initials: N
authors.lastname: Gallego
authors.forename: Liliana
authors.initials: L
authors.lastname: Franco
authors.forename: Arti
authors.initials: A
authors.lastname: Tandon
authors.forename: Tábita
authors.initials: T
authors.lastname: Hünemeier
authors.forename: Cátira
authors.initials: C
authors.lastname: Bortolini
authors.forename: Alberto
authors.initials: A
authors.lastname: Villegas
authors.forename: Gabriel
authors.initials: G
authors.lastname: Bedoya
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
authors.forename: Alkes
authors.initials: A
authors.lastname: Price
authors.forename: David
authors.initials: D
authors.lastname: Reich
authors.forename: Andrés
authors.initials: A
authors.lastname: Ruiz-Linares
mesh_terms: D000483:Alleles; D015992:Body Mass Index; D016022:Case-Control Studies; D003105:Colombia / Q000453:epidemiology / Q000208:ethnology; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D005787:Gene Frequency; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007199:Indians, South American / Q000235:genetics*; D008126:Lod Score; D020641:Polymorphism, Single Nucleotide; D012923:Social Class