https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51617 Wed 28 Feb 2024 16:00:51 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45560 Wed 28 Feb 2024 15:21:35 AEDT ]]> https://ogma.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://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45264 Wed 26 Oct 2022 18:09:09 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48511 n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.]]> Wed 22 Mar 2023 15:25:15 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41782  0.05). Our findings suggest that the inverse association of birthweight with hypertension risk from observational studies was not supported by large Mendelian randomization analyses.]]> Wed 22 Mar 2023 14:30:25 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51038 P = 1.098 × 10^-8) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits.]]> Wed 16 Aug 2023 10:23:55 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51039 -2, threshold = 2.5 × 10^-2). For the GenLang Cohort (n = 26,558), SNPs in DOCK7 and CDH4 showed significant association for the NM/AG hypothesis (sFDR q = 1.02 × 10^-2). To make the GenLang dataset more similar to Toronto, we repeated the analysis restricting to samples selected for reading/language deficits (n = 4152). In this GenLang selected subset, we found significant association for a locus intergenic between BTG3-C21orf91 for both hypotheses (sFDR q < 9.00 × 10^-4). This study contributes candidate loci to the genetics of word reading. Data also suggest that, although different variants may be involved, alleles implicated in ASD risk may be found in the same genes as those implicated in word reading. This finding is limited to the Toronto sample suggesting that ascertainment influences genetic associations.]]> Wed 16 Aug 2023 10:23:40 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52463 Wed 11 Oct 2023 15:07:44 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44767 Tue 30 May 2023 11:48:47 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50431 Tue 25 Jul 2023 19:01:27 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50411 Tue 25 Jul 2023 17:30:33 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53968 Tue 23 Jan 2024 15:33:56 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53962 Tue 23 Jan 2024 12:39:27 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53295 Tue 21 Nov 2023 11:54:41 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44364 Tue 21 Mar 2023 17:38:16 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52573 Tue 17 Oct 2023 15:48:00 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53822 Tue 16 Jan 2024 15:19:57 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48599 Tue 04 Apr 2023 19:22:25 AEST ]]> https://ogma.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://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:39188 P=0.009), and at the inferotemporal (P=0.015), superotemporal (P=0.044), and temporal sectors (P=0.046). Lower adrenal sensitivity was associated with thinner RNFL inferotemporally (P<0.001) and temporally (P=0.037). However, these effect sizes were small; for example, a 10 pg/mL increase in baseline ACTH was associated with only a 3 µm thinner RNFL. RNFL thickness was not associated with plasma cortisol levels and or significantly different between groups of acute stress response patterns. Conclusions: Although there was a link between ACTH or adrenal sensitivity and RNFL thickness, this association was weak and its clinical significance is unclear. Despite the close associations between levels of endogenous stress markers and IOP, we found limited evidence of a link to RNFL integrity.]]> Thu 26 May 2022 09:15:19 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54919 Thu 21 Mar 2024 13:13:19 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:39755 Thu 21 Jul 2022 09:10:24 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41704 -7). Comparison of exome array variants to regional linkage disequilibrium (LD) patterns and prior genome-wide association study (GWAS) results detected candidate variants (r² > .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p < 1 x 10^-4) with at least one obesity or lipid trait. Candidate genes include PRKAR2A, PTH1R, and HDAC9, which have been suggested to play roles in adipocyte differentiation or bone marrow adipose tissue. Taken together, these findings provide further insights into the processes that influence circulating adiponectin levels.]]> Thu 11 Aug 2022 15:21:17 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:46927 Thu 08 Dec 2022 12:22:07 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36340 Thu 02 Mar 2023 14:17:32 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48123 Thu 02 Mar 2023 14:17:32 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40140 Mon 25 Jul 2022 09:00:17 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:42033 Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.]]> Mon 22 Aug 2022 10:16:20 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48483 LCT-13910 C/T, rs4988235) associated with dairy intake as an instrumental variable (IV). The causal effects of dairy intake on body composition and cardiometabolic traits (lipids, glycemic traits, and inflammatory factors) were quantified by IV estimators among 182041 participants from 18 studies. Results: Each 1 serving/day higher dairy intake was associated with higher lean mass [β (SE) = 0.117 kg (0.035); P = 0.001], higher hemoglobin A1c [0.009% (0.002); P < 0.001], lower LDL [-0.014 mmol/L (0.006); P = 0.013], total cholesterol (TC) [-0.012 mmol/L (0.005); P = 0.023], and non-HDL [-0.012 mmol/L (0.005); P = 0.028]. The LCT-13910 C/T CT + TT genotype was associated with 0.214 more dairy servings/day (SE = 0.047; P < 0.001), 0.284 cm higher waist circumference (SE = 0.118; P = 0.017), 0.112 kg higher lean mass (SE = 0.027; P = 3.8 x 10-5), 0.032 mmol/L lower LDL (SE = 0.009; P = 0.001), and 0.032 mmol/L lower TC (SE = 0.010; P = 0.001). Genetically higher dairy intake was associated with increased lean mass [0.523 kg per serving/day (0.170); P = 0.002] after correction for multiple testing (0.05/18). However, we find that genetically higher dairy intake was not associated with lipids and glycemic traits. Conclusions: The present study provides evidence to support a potential causal effect of higher dairy intake on increased lean mass among adults. Our findings suggest that the observational associations of dairy intake with lipids and glycemic traits may be the result of confounding.]]> Mon 20 Mar 2023 10:41:47 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50974 Mon 14 Aug 2023 15:18:04 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54727 Mon 11 Mar 2024 14:11:41 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52326 Mon 09 Oct 2023 10:23:49 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41061 HHIP) gene and was previously associated with lung function and HHIP lung expression. We found HHIP expression was significantly different between the sexes (P=6.90x10⁻⁶), but we could not detect sex differential effects of rs7697189 on expression. Conclusions: We identified a novel genotype-by-sex interaction at a putative enhancer region upstream of the HHIP gene. Establishing the mechanism by which HHIP SNPs have different effects on lung function in males and females will be important for our understanding of lung health and diseases in both sexes.]]> Fri 22 Jul 2022 13:18:47 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:39168 Fri 20 May 2022 16:24:36 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50835 Fri 18 Aug 2023 10:27:30 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53055 Fri 17 Nov 2023 11:47:02 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:39717 Fri 17 Jun 2022 17:31:05 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41849 Fri 12 Aug 2022 15:46:58 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41815 Fri 12 Aug 2022 12:45:25 AEST ]]> https://ogma.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 ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:55053 Fri 05 Apr 2024 09:56:04 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:39716 Fri 02 Jun 2023 09:38:38 AEST ]]>