https://novaprd-lb.newcastle.edu.au/vital/access/manager/Index en-au 5 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:48519 p = 1.3 x 10⁻⁴) for all ischemic stroke, 0.63 (95% CI 0.50–0.80; p = 1.6 x 10⁻⁴) for cardioembolic stroke, and 0.60 (95% CI 0.44–0.82; p = 0.001) for large artery stroke; there was no association with small vessel stroke (odds ratio 0.90, 95% CI 0.67–1.20; p = 0.46). Only the association with cardioembolic stroke was robust in sensitivity analyses. There was no association of genetically predicted serum calcium concentrations with all ischemic stroke (per 0.5 mg/dL [about 1 SD] increase in serum calcium: odds ratio 1.03, 95% CI 0.88–1.21) or with any subtype. Conclusions: This study found that genetically higher serum magnesium concentrations are associated with a reduced risk of cardioembolic stroke but found no significant association of genetically higher serum calcium concentrations with any ischemic stroke subtype.]]> Wed 22 Mar 2023 17:11:50 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:50431 Tue 25 Jul 2023 19:01:27 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:47666 Tue 24 Jan 2023 15:47:40 AEDT ]]> 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:53055 Fri 17 Nov 2023 11:47:02 AEDT ]]>