Replication of genetic variants from genome-wide association studies with metabolic traits in an island population of the Adriatic coast of Croatia

Rebekah Karns, Ge Zhang, Nina Jeran, Dubravka Havas-Augustin, Sasa Missoni, Wen Niu, Subba Rao Indugula, Guangyun Sun, Zijad Durakovic, Nina Smolej Narancic, Pavao Rudan, Ranajit Chakraborty, Ranjan Deka

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15 Scopus citations

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.

Original languageEnglish
Pages (from-to)341-346
Number of pages6
JournalEuropean Journal of Human Genetics
Volume19
Issue number3
DOIs
StatePublished - Mar 2011

Keywords

  • FTO
  • TCF7L2
  • genetic association
  • isolated population
  • obesity
  • type 2 diabetes

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    Karns, R., Zhang, G., Jeran, N., Havas-Augustin, D., Missoni, S., Niu, W., Indugula, S. R., Sun, G., Durakovic, Z., Narancic, N. S., Rudan, P., Chakraborty, R., & Deka, R. (2011). Replication of genetic variants from genome-wide association studies with metabolic traits in an island population of the Adriatic coast of Croatia. European Journal of Human Genetics, 19(3), 341-346. https://doi.org/10.1038/ejhg.2010.178