Assessment of polygenic effects links primary open-angle glaucoma and age-related macular degeneration
Gabriel Cuellar-Partida,Jamie E Craig,Kathryn P. Burdon,Jie Jin Wang,Brendan J Vote,Emmanuelle Souzeau,Ian L. McAllister,Timothy Isaacs,Stewart Lake,David A. Mackey,David A. Mackey,Ian J. Constable,Paul Mitchell,Alex W. Hewitt,Alex W. Hewitt,Stuart MacGregor +15 more
TL;DR: The genetic architecture of POAG and AMD is investigated using genome-wide array data and it is found that the genetic correlation between sexes for POAG was likely to be less than 1, suggesting that differences of prevalence among genders may be partly due to heritable factors.
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Abstract: Primary open-angle glaucoma (POAG) and age-related macular degeneration (AMD) are leading causes of irreversible blindness. Several loci have been mapped using genome-wide association studies. Until very recently, there was no recognized overlap in the genetic contribution to AMD and POAG. At genome-wide significance level, only ABCA1 harbors associations to both diseases. Here, we investigated the genetic architecture of POAG and AMD using genome-wide array data. We estimated the heritability for POAG (h2g = 0.42 ± 0.09) and AMD (h2g = 0.71 ± 0.08). Removing known loci for POAG and AMD decreased the h2g estimates to 0.36 and 0.24, respectively. There was evidence for a positive genetic correlation between POAG and AMD (rg = 0.47 ± 0.25) which remained after removing known loci (rg = 0.64 ± 0.31). We also found that the genetic correlation between sexes for POAG was likely to be less than 1 (rg = 0.33 ± 0.24), suggesting that differences of prevalence among genders may be partly due to heritable factors.
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References
An integrated map of genetic variation from 1,092 human genomes
Gonçalo R. Abecasis,Adam Auton,Lisa D. Brooks,Mark A. DePristo,Richard Durbin,Robert E. Handsaker,Robert E. Handsaker,Hyun Min Kang,Gabor T. Marth,Gil McVean +9 more
TL;DR: It is shown that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites.
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TL;DR: The GCTA software is a versatile tool to estimate and partition complex trait variation with large GWAS data sets and focuses on the function of estimating the variance explained by all the SNPs on the X chromosome and testing the hypotheses of dosage compensation.
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Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis.
TL;DR: The global prevalence of primary open-angle glaucoma (POAG) and primary angle-closure glauComa (PACG) and the number of affected people in 2020 and 2040 are examined, disproportionally affecting people residing in Asia and Africa.
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LD score regression distinguishes confounding from polygenicity in genome-wide association studies :
Brendan Bulik-Sullivan,Po-Ru Loh,Hilary K. Finucane,Stephan Ripke,Jian Yang,Nick Patterson,Mark J. Daly,Alkes L. Price,Benjamin M. Neale +8 more
TL;DR: It is found that polygenicity accounts for the majority of the inflation in test statistics in many GWAS of large sample size, and the LD Score regression intercept can be used to estimate a more powerful and accurate correction factor than genomic control.
Common SNPs explain a large proportion of the heritability for human height
Jian Yang,Beben Benyamin,Brian P. McEvoy,Scott D. Gordon,Anjali K. Henders,Dale R. Nyholt,Pamela A. F. Madden,Andrew C. Heath,Nicholas G. Martin,Grant W. Montgomery,Michael E. Goddard,Peter M. Visscher +11 more
TL;DR: Evidence is provided that the remaining heritability is due to incomplete linkage disequilibrium between causal variants and genotyped SNPs, exacerbated by causal variants having lower minor allele frequency than the SNPs explored to date.
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