https://novaprd-lb.newcastle.edu.au/vital/access/manager/Index ${session.getAttribute("locale")} 5 https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:48705 Wed 29 Mar 2023 17:38:49 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:49987 Wed 28 Feb 2024 16:27:03 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:50431 Wed 28 Aug 2024 15:49:50 AEST ]]> https://novaprd-lb.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://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:48569 Wed 22 Mar 2023 15:26:43 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:42676 Wed 22 Mar 2023 14:34:07 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:51667 2) based on acute neuroimaging data in a Bayesian hierarchical framework. Lesions encompassing bilateral subcortical nuclei and left-lateralized regions in proximity to the insula explained outcomes across men and women (area under the curve = 0.81). A pattern of left-hemispheric posterior circulation brain regions, combining left hippocampus, precuneus, fusiform and lingual gyrus, occipital pole and latero-occipital cortex, showed a substantially higher relevance in explaining functional outcomes in women compared to men [mean difference of Bayesian posterior distributions (men – women) = −0.295 (90% highest posterior density interval = −0.556 to −0.068)]. Once validated in prospective studies, our findings may motivate a sex-specific approach to clinical stroke management and hold the promise of enhancing outcomes on a population level.]]> Wed 13 Sep 2023 10:08:36 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:52000 Tue 26 Sep 2023 11:29:09 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:51991 Tue 26 Sep 2023 11:00:58 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:50411 Tue 25 Jul 2023 17:30:33 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:43840 Tue 21 Mar 2023 17:30:07 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:39658 Tue 21 Mar 2023 17:22:55 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:51452 2) were modeled within purpose-built Bayesian linear and logistic regression frameworks. Interaction effects between stroke lesions and a high vs low WMH burden were integrated via hierarchical model structures. Models were adjusted for age, age2, sex, total DWI lesion and WMH volumes, and comorbidities. Data were split into derivation and validation cohorts. Results: A total of 928 patients with AIS contributed to acute stroke severity analyses (age: 64.8 [14.5] years, 40% women) and 698 patients to long-term functional outcome analyses (age: 65.9 [14.7] years, 41% women). Stroke severity was mainly explained by lesions focused on bilateral subcortical and left hemispherically pronounced cortical regions across patients with both a high and low WMH burden. Lesions centered on left-hemispheric insular, opercular, and inferior frontal regions and lesions affecting right-hemispheric temporoparietal regions had more pronounced effects on stroke severity in case of high compared with low WMH burden. Unfavorable outcomes were predominantly explained by lesions in bilateral subcortical regions. In difference to the lesion location–specific WMH effects on stroke severity, higher WMH burden increased the odds of unfavorable outcomes independent of lesion location. Discussion: Higher WMH burden may be associated with an increased stroke severity in case of stroke lesions involving left-hemispheric insular, opercular, and inferior frontal regions (potentially linked to language functions) and right-hemispheric temporoparietal regions (potentially linked to attention). Our findings suggest that patients with specific constellations of WMH burden and lesion locations may have greater benefits from acute recanalization treatments. Future clinical studies are warranted to systematically assess this assumption and guide more tailored treatment decisions.]]> Tue 05 Sep 2023 18:01:19 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:48599 Tue 04 Apr 2023 19:22:25 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:30822 50 loci at which common variants with minor allele frequency >5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 × 10−8 previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until whole-genome sequencing becomes feasible in large samples.]]> Tue 04 Apr 2023 19:09:51 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:41379 Tue 04 Apr 2023 19:08:51 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:52122  2) was modeled in a Bayesian logistic regression framework. Effects of individual brain regions were captured as two compound effects for (i) six bilateral rich club and (ii) all further non-rich club regions. In spatial specificity analyses, we randomized the split into "rich club" and "non-rich club" regions and compared the effect of the actual rich club regions to the distribution of effects from 1000 combinations of six random regions. In sex-specific analyses, we introduced an additional hierarchical level in our model structure to compare male and female-specific rich club effects. A total of 822 patients (age: 64.7[15.0], 39% women) were analyzed. Rich club regions had substantial relevance in explaining unfavorable functional outcome (mean of posterior distribution: 0.08, area under the curve: 0.8). In particular, the rich club-combination had a higher relevance than 98.4% of random constellations. Rich club regions were substantially more important in explaining long-term outcome in women than in men. All in all, lesions in rich club regions were associated with increased odds of unfavorable outcome. These effects were spatially specific and more pronounced in women.]]> Thu 28 Sep 2023 15:03:53 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:55454 Mon 03 Jun 2024 08:45:08 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:55383 Fri 24 May 2024 10:35:40 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:53055 Fri 17 Nov 2023 11:47:02 AEDT ]]>