https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47878 Wed 28 Feb 2024 14:58:48 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47731 g| ~ 0.25 to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near SNPs associated with general risk tolerance are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We found no evidence of enrichment for genes previously hypothesized to relate to risk tolerance.]]> Wed 25 Jan 2023 14:39:42 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42468 Wed 24 Aug 2022 11:40:43 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44073 Wed 22 Mar 2023 15:46:47 AEDT ]]> https://nova.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://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33058 Wed 15 Dec 2021 16:09:20 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27984 Wed 15 Dec 2021 16:06:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47126 Wed 14 Dec 2022 14:45:32 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:14264 −11) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10⁻⁹), ANK3 (rs10994359, P = 2.5 × 10⁻⁸) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10⁻⁹).]]> Wed 11 Apr 2018 18:45:05 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29536 Wed 11 Apr 2018 15:45:41 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49007 Wed 03 May 2023 12:17:36 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53968 Wed 03 Jul 2024 10:04:32 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47666 Tue 24 Jan 2023 15:47:40 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53295 Tue 21 Nov 2023 11:54:41 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41408 Tue 21 Mar 2023 18:03:04 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:39718 270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15-17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype-phenotype map than previously anticipated.]]> Tue 21 Mar 2023 17:20:57 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42894 Tue 06 Sep 2022 14:32:21 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34283 −15), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 × 10⁻⁶). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 × 10⁻¹¹) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 × 10⁻⁵). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by nonallelic homologous recombination.]]> Tue 03 Sep 2019 18:30:49 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51182 Tue 03 Oct 2023 19:34:38 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53505 Thu 30 Nov 2023 15:57:26 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33786 -8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.]]> Thu 30 Mar 2023 15:49:49 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50043 Thu 29 Jun 2023 14:38:49 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46927 Thu 08 Dec 2022 12:22:07 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:7518 Sat 24 Mar 2018 08:38:28 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:7942 Sat 24 Mar 2018 08:34:59 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13924 −11, odds ratio (OR) = 1.32), with the A allele (coding for histadine) conferring elevated disease risk. The second locus is at 19q13, (P = 2.51 x 10⁻⁹, OR = 1.42 for the rs2233152 SNP near MIA and RAB4B; P = 1.68 x 10⁻¹², OR = 1.52 for rs28493229 in ITPKC), which confirms previous findings¹. The involvement of the FCGR2A locus may have implications for understanding immune activation in Kawasaki disease pathogenesis and the mechanism of response to intravenous immunoglobulin, the only proven therapy for this disease.]]> Sat 24 Mar 2018 08:24:48 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17125 −10) that is also associated with risk of prostate cancer and is inversely associated with risk of type 2 diabetes.]]> Sat 24 Mar 2018 08:02:31 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21864 Sat 24 Mar 2018 07:59:11 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21233 P < 5 × 10⁻⁸) with FVC in or near EFEMP1, BMP6, MIR129-2–HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.]]> Sat 24 Mar 2018 07:53:01 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21532 −3), and we confirm association of rs7521902 at 1p36.12 near WNT4. In addition, we establish an association of rs13394619 in GREB1 at 2p25.1 with endometriosis and identify a newly associated locus at 12q22 near VEZT (rs10859871). Excluding cases of European ancestry of minimal or unknown severity, we identified additional previously unknown loci at 2p14 (rs4141819), 6p22.3 (rs7739264) and 9p21.3 (rs1537377). All seven SNP effects were replicated in an independent cohort and associated at P <5 × 10⁻⁸ in a combined analysis. Finally, we found a significant overlap in polygenic risk for endometriosis between the genome-wide association cohorts of European and Japanese descent (P = 8.8 × 10⁻¹¹), indicating that many weakly associated SNPs represent true endometriosis risk loci and that risk prediction and future targeted disease therapy may be transferred across these populations.]]> Sat 24 Mar 2018 07:50:27 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:25277 −11; odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28–1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes.]]> Sat 24 Mar 2018 07:38:17 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30267 n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρˆ| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.]]> Sat 24 Mar 2018 07:33:37 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28937 Sat 24 Mar 2018 07:31:27 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28431 140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.]]> Sat 24 Mar 2018 07:29:03 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28311 Sat 24 Mar 2018 07:27:06 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:23305 Sat 24 Mar 2018 07:16:19 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:23306 Sat 24 Mar 2018 07:16:19 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:23578 −4). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 x 10⁻⁸), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.]]> Sat 24 Mar 2018 07:12:44 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:24712 Sat 24 Mar 2018 07:11:04 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47780 Mon 30 Jan 2023 10:58:57 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13951 Mon 26 Aug 2024 14:20:06 AEST ]]> https://nova.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://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20652 Mon 14 Dec 2020 14:04:44 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50972 Mon 14 Aug 2023 15:19:39 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46970 Mon 12 Dec 2022 16:19:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:55383 Fri 24 May 2024 10:35:40 AEST ]]>