@article{3056660,
    title = "Evaluating the glucose raising effect of established loci via a genetic risk score",
    author = "Marouli, E. and Kanoni, S. and Mamakou, V. and Hackinger, S. and Southam, L. and Prins, B. and Rentari, A. and Dimitriou, M. and Zengini, E. and Gonidakis, F. and Kolovou, G. and Kontaxakis, V. and Rallidis, L. and Tentolouris, N. and Thanopoulou, A. and Lamnissou, K. and Dedoussis, G. and Zeggini, E. and Deloukas, P.",
    journal = "PLOS ONE",
    year = "2017",
    volume = "12",
    number = "11",
    publisher = "Public Library of Science",
    doi = "10.1371/journal.pone.0186669",
    keywords = "alpha 2A adrenergic receptor;  glucose;  protein G6PC2;  protein LPIN3;  protein MTNR1B;  protein PROX1;  protein SLC30A8;  unclassified drug, adult;  Article;  gene locus;  genetic risk score;  genetic variability;  Greek (people);  human;  meta analysis (topic);  middle aged;  population research;  scoring system;  female;  genetic predisposition;  genome-wide association study;  glucose blood level;  male;  metabolism;  single nucleotide polymorphism, Blood Glucose;  Female;  Genetic Predisposition to Disease;  Genome-Wide Association Study;  Humans;  Male;  Polymorphism, Single Nucleotide",
    abstract = "Recent genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with glucose levels. We tested the hypothesis here whether the cumulative effect of glucose raising SNPs, assessed via a score, is associated with glucose levels. A total of 1,434 participants of Greek descent from the THISEAS study and 1,160 participants form the GOMAP study were included in this analysis. We developed a genetic risk score (GRS), based on the known glucose-raising loci, in order to investigate the cumulative effect of known glucose loci on glucose levels. In the THISEAS study, the GRS score was significantly associated with increased glucose levels (mmol/L) (β ± SE: 0.024 ± 0.004, P = 8.27e-07). The effect of the genetic risk score was also significant in the GOMAP study (β ± SE: 0.011 ± 0.005, P = 0.031). In the meta-analysis of the two studies both scores were significantly associated with higher glucose levels GRS: β ± SE: 0.019 ± 0.003, P = 1.41e-09. Also, variants at the SLC30A8, PROX1, MTNR1B, ADRA2A, G6PC2, LPIN3 loci indicated nominal evidence for association with glucose levels (p < 0.05). We replicate associations of the established glucose raising variants in the Greek population and confirm directional consistency of effects (binomial sign test p = 6.96e-05). We also demonstrate that the cumulative effect of the established glucose loci yielded a significant association with increasing glucose levels. © 2017 Marouli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited."
}