The candidate genes TAF5L, TCF7, PDCD1, IL6 and ICAM1 cannot be excluded from having effects in type 1 diabetes
BMC MEDICAL GENETICS
Authors: Cooper, Jason D.; Smyth, Deborah J.; Bailey, Rebecca; Payne, Felicity; Downes, Kate; Godfrey, Lisa M.; Masters, Jennifer; Zeitels, Lauren R.; Vella, Adrian; Walker, Neil M.; Todd, John A.
Background: As genes associated with immune-mediated diseases have an increased prior probability of being associated with other immune-mediated diseases, we tested three such genes, IL23R, IRF5 and CD40, for an association with type 1 diabetes. In addition, we tested seven genes, TAF5L, PDCD1, TCF7, IL12B, IL6, ICAM1 and TBX21, with published marginal or inconsistent evidence of an association with type 1 diabetes. Methods: We genotyped reported polymorphisms of the ten genes, nonsynonymous SNPs (nsSNPs) and, for the IL12B and IL6 regions, tag SNPs in up to 7,888 case, 8,858 control and 3,142 parent-child trio samples. In addition, we analysed data from the Wellcome Trust Case Control Consortium genome-wide association study to determine whether there was any further evidence of an association in each gene region. Results: We found some evidence of associations between type 1 diabetes and TAF5L, PDCD1, TCF7 and IL6 (ORs = 1.05 - 1.13; P = 0.0291 - 4.16 x 10(-4)). No evidence of an association was obtained for IL12B, IRF5, IL23R, ICAM1, TBX21 and CD40, although there was some evidence of an association (OR = 1.10; P = 0.0257) from the genome-wide association study for the ICAM1 region. Conclusion: We failed to exclude the possibility of some effect in type 1 diabetes for TAF5L, PDCD1, TCF7, IL6 and ICAM1. Additional studies, of these and other candidate genes, employing much larger sample sizes and analysis of additional polymorphisms in each gene and its flanking region will be required to ascertain their contributions to type 1 diabetes susceptibility.
Parent and offspring genotypes influence gene expression in early life
Authors: Newhouse, Daniel J.; Barcelo-Serra, Margarida; Tuttle, Elaina M.; Gonser, Rusty A.; Balakrishnan, Christopher N.
Parents can have profound effects on offspring fitness. Little, however, is known about the mechanisms through which parental genetic variation influences offspring physiology in natural systems. White-throated sparrows (Zonotrichia albicollis, WTSP) exist in two genetic morphs, tan and white, controlled by a large polymorphic supergene. Morphs mate disassortatively, resulting in two pair types: tan male x white female (T x W) pairs, which provide biparental care and white male x tan female (W x T) pairs, which provide female-biased care. To investigate how parental composition impacts offspring, we performed RNA-seq on whole blood of WTSP nestlings sampled from nests of both pair types. Parental pair type had a large effect on nestling gene expression, with 881 genes differentially expressed (DE) and seven correlated gene coexpression modules. The DE genes and modules expressed at higher levels in W x T nests with female-biased parental care function in metabolism and stress-related pathways resulting from the overrepresentation of proteolysis and stress-response genes (e.g., SOD2, NR3C1). These results show that parental genotypes and/or associated behaviours influence nestling physiology, and highlight avenues of further research investigating the ultimate implications for the maintenance of this polymorphism. Nestlings also exhibited morph-specific gene expression, with 92 differentially expressed genes, comprising immunity genes and genes encompassed by the supergene. Remarkably, we identified the same regulatory hub genes in these blood-derived expression networks as were previously identified in adult WTSP brains (EPM2A, BPNT1, TAF5L). These hub genes were located within the supergene, highlighting the importance of this gene complex in structuring regulatory networks across diverse tissues.