Genome-wide association (GWA) studies represent a powerful approach to the identification of genes involved in common human diseases. In this report, we describe a GWA study (using Affymetrix Genome-Wide Human SNP Array 5.0) of Metabolic Syndrome (MetS) and related quantitative traits (including 15 anthropometric and 11 blood biochemical traits) in a sample of ~1, 500 individuals drawn from a homogenous population of Hvar Island off the eastern Adriatic coast of Croatia. Association tests of quantitative traits identified a large number of independent association signals (with single-point P values less than 10-6). These signals include many previously reported loci such as SLC2A9 (uric acid), TCF7L2 (FBG and HbA1c), CETP (HDL), HMGA2 and UQCC (body height) as well as some novel loci which may represent genuine effects. Some notable examples include: rs17154194 (intergenic SNP) was associated with FBG (P = 2.8×10-9) and triglyceride (P = 2.4×10-8) ; rs200116 (downstream of SEMA5A) and rs833820 (intron of ARF3) were associated with uric acid (P = 3.7×10-8 and 9.2×10-8) ; rs11030796 (intron of STIM1) was associated with fibrinogen (P = 1.8×10-8) ; rs3746410 (FER1L4) was associated with body weight (P = 1.2×10-6). We also detected rs1521282 (downstream of CPNE4) as a susceptibility locus for MetS as a binary trait by either ATP (P = 1.1×10-7) or IDF (P = 3.6×10-6) definition. In addition, using a principle component analysis of the quantitative traits used in MetS diagnostic criteria (waist circumference, triglyceride, HDL, blood pressure and FBG), we observed several genes implicated in blood glucose homeostasis (KCNJ11, TCF7L2, SLC30A8 and FBP2) were associated independently with individual principle components of MetS traits. In summary, our study yield additional genetic loci that may influence MetS susceptibility or related quantitative traits. These findings were either supported by high-level of statistical significance and/or functional implications which make them highly interesting for further replication and follow-up. Our results also suggest that the genes involved in blood glucose homeostasis may play important role in the development of MetS.

Biologija,Etnologija i antropologija