title: Replication of genetic variants from genome-wide association studies with metabolic traits in an island population of the Adriatic coast of Croatia.
abstract: Twenty-two single-nucleotide polymorphisms (SNPs) in 10 gene regions previously identified in obesity and type 2 diabetes (T2D) genome-wide association studies (GWAS) were evaluated for association with metabolic traits in a sample from an island population of European descent. We performed a population-based study using 18 anthropometric and biochemical traits considered as continuous variables in a sample of 843 unrelated subjects (360 men and 483 women) aged 18-80 years old from the island of Hvar on the eastern Adriatic coast of Croatia. All eight GWAS SNPs in FTO were significantly associated with weight, body mass index, waist circumference and hip circumference; 20 of the 32 nominal P-values remained significant after permutation testing for multiple corrections. The strongest associations were found between the two TCF7L2 GWAS SNPs with fasting plasma glucose and HbA1c levels, all four P-values remained significant after permutation tests. Nominally significant associations were found between several SNPs and other metabolic traits; however, the significance did not hold after permutation tests. Although the sample size was modest, our study strongly replicated the association of FTO variants with obesity-related measures and TCF7L2 variants with T2D-related traits. The estimated effect sizes of these variants were larger or comparable to published studies. This is likely attributable to the homogenous genetic background of the relatively isolated study population.
authors.affiliation: Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0056, USA.
authors.forename: Rebekah
authors.initials: R
authors.lastname: Karns
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.forename: Nina
authors.initials: N
authors.lastname: Jeran
authors.forename: Dubravka
authors.initials: D
authors.lastname: Havas-Augustin
authors.forename: Sasa
authors.initials: S
authors.lastname: Missoni
authors.forename: Wen
authors.initials: W
authors.lastname: Niu
authors.forename: Subba Rao
authors.initials: SR
authors.lastname: Indugula
authors.forename: Guangyun
authors.initials: G
authors.lastname: Sun
authors.forename: Zijad
authors.initials: Z
authors.lastname: Durakovic
authors.forename: Nina Smolej
authors.initials: NS
authors.lastname: Narancic
authors.forename: Pavao
authors.initials: P
authors.lastname: Rudan
authors.forename: Ranajit
authors.initials: R
authors.lastname: Chakraborty
authors.forename: Ranjan
authors.initials: R
authors.lastname: Deka
mesh_terms: D000328:Adult; D000368:Aged; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D001835:Body Weight; D017523:Croatia; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D005843:Geography; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D044382:Population Groups; D011506:Proteins / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*; D055105:Waist Circumference
chemical_list: D011506:Proteins; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human