Identification of candidate genes in the type 2 diabetes modifier locus using expression QTL.

To identify new genetic determinants relevant to type 2 diabetes (T2D), diabetic F2 progeny were generated by intercrossing F1 mice obtained from a cross of BKS.Cg-Lepr db +/+m and DBA/2, and T2D-related phenotypes were measured. In the F2 population, increased susceptibilitytodiabetesandobesitywasobserved.Wealsodetectedthemajorquantitativetraitloci(QTL)modifyingtheseverityofdiabeteson chromosome 9, where peaks of logarithm of odds (LOD) overlapped for three traits. To identify candidate genes in the QTL intervals, we combined bexpression QTLQ (eQTL), taking mRNA levels as quantitative traits, and binterstrain sequence variations, including cSNPs.Q As a result,fourgeneswereidentifiedfromcosegregationofclinicalQTLwitheQTLand13geneswerefoundfrominterstraincSNPsascandidatesin the T2D modifier QTL. Our combined approach shows the acceleration of the discovery of candidate genes in the QTL of interest, spanning several megabases.