https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45256 1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.]]> Wed 26 Oct 2022 20:06:39 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:52463 Wed 11 Oct 2023 15:07:44 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45201 P = 3.96 x 10^-14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.]]> Thu 27 Oct 2022 15:06:39 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54727 Mon 11 Mar 2024 14:11:41 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41815 Fri 12 Aug 2022 12:45:25 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46943 METTL15). The variant was nominally associated with only the European subgroup analysis but had a consistent direction of effect in other ethnicities. We then utilized trans-ancestral Bayesian analysis to narrow down the location of the probable causal variant at each genome-wide significant signal. Of all the fine-mapped loci, we were able to narrow down the causative variant at four known loci to fewer than 10 single nucleotide polymorphisms (SNPs) (FAIM2, GNPDA2, MC4R and SEC16B loci). In conclusion, an ethnically diverse setting has enabled us to both identify an additional pediatric obesity locus and further fine-map existing loci.]]> Fri 09 Dec 2022 14:01:32 AEDT ]]>