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:50431 Tue 25 Jul 2023 19:01:27 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50411 Tue 25 Jul 2023 17:30:33 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48599 Tue 04 Apr 2023 19:22:25 AEST ]]> https://nova.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://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:23785 5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.]]> Sat 24 Mar 2018 07:16:26 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53055 Fri 17 Nov 2023 11:47:02 AEDT ]]>