Underlying genetic models of inheritance in established type 2 diabetes associations.
For most associations of common single nucleotide polymorphisms (SNPs) with common diseases, the genetic model of inheritance is unknown. The authors extended and applied a Bayesian meta-analysis approach to data from 19 studies on 17 replicated associations with type 2 diabetes. For 13 SNPs, the data fitted very well to an additive model of inheritance for the diabetes risk allele; for 4 SNPs, the data were consistent with either an additive model or a dominant model; and for 2 SNPs, the data were consistent with an additive or recessive model. Results were robust to the use of different priors and after exclusion of data for which index SNPs had been examined indirectly through proxy markers. The Bayesian meta-analysis model yielded point estimates for the genetic effects that were very similar to those previously reported based on fixed- or random-effects models, but uncertainty about several of the effects was substantially larger. The authors also examined the extent of between-study heterogeneity in the genetic model and found generally small between-study deviation values for the genetic model parameter. Heterosis could not be excluded for 4 SNPs. Information on the genetic model of robustly replicated association signals derived from genome-wide association studies may be useful for predictive modeling and for designing biologic and functional experiments.
Salanti
Georgia
G
Clinical and Molecular Epidemiology Unit and Clinical Trials and Evidence-Based Medicine Unit, Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece.
Southam
Lorraine
L
Altshuler
David
D
Ardlie
Kristin
K
Barroso
Inês
I
Boehnke
Michael
M
Cornelis
Marilyn C
MC
Frayling
Timothy M
TM
Grallert
Harald
H
Grarup
Niels
N
Groop
Leif
L
Hansen
Torben
T
Hattersley
Andrew T
AT
Hu
Frank B
FB
Hveem
Kristian
K
Illig
Thomas
T
Kuusisto
Johanna
J
Laakso
Markku
M
Langenberg
Claudia
C
Lyssenko
Valeriya
V
McCarthy
Mark I
MI
Morris
Andrew
A
Morris
Andrew D
AD
Palmer
Colin N A
CN
Payne
Felicity
F
Platou
Carl G P
CG
Scott
Laura J
LJ
Voight
Benjamin F
BF
Wareham
Nicholas J
NJ
Zeggini
Eleftheria
E
Ioannidis
John P A
JP
D001499:Bayes Theorem; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*