TY - JOUR
T1 - Evaluating the glucose raising effect of established loci via a genetic risk score
AU - Marouli, Eirini
AU - Kanoni, Stavroula
AU - Mamakou, Vasiliki
AU - Hackinger, Sophie
AU - Southam, Lorraine
AU - Prins, Bram
AU - Rentari, Angela
AU - Dimitriou, Maria
AU - Zengini, Eleni
AU - Gonidakis, Fragiskos
AU - Kolovou, Genovefa
AU - Kontaxakis, Vassilis
AU - Rallidis, Loukianos
AU - Tentolouris, Nikolaos
AU - Thanopoulou, Anastasia
AU - Lamnissou, Klea
AU - Dedoussis, George
AU - Zeggini, Eleftheria
AU - Deloukas, Panagiotis
N1 - Publisher Copyright:
© 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.
PY - 2017/11
Y1 - 2017/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85033603016&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0186669
DO - 10.1371/journal.pone.0186669
M3 - Article
C2 - 29125842
AN - SCOPUS:85033603016
SN - 1932-6203
VL - 12
JO - PLoS ONE
JF - PLoS ONE
IS - 11
M1 - e0186669
ER -