Expressive

rs10869665 - PCSK5

Magnitude 2.0 · 4 studies on file

Reported associations

  • Large-scale multitrait genome-wide association analyses identify hundreds of glaucoma risk loci - Nature genetics (2023) · Han X, Gharahkhani P, Hamel AR, Ong JS, Rentería ME, Mehta P, Dong X, Pasutto F, Hammond C, Young TL, Hysi P, Lotery AJ, Jorgenson E, Choquet H, Hauser M, Cooke Bailey JN, Nakazawa T, Akiyama M, Shiga Y, Fuller ZL, Wang X, Hewitt AW, Craig JE, Pasquale LR, Mackey DA, Wiggs JL, Khawaja AP, Segrè AV, MacGregor S · PubMed 37386247

    ABSTRACT: Glaucoma, a leading cause of irreversible blindness, is a highly heritable human disease. Previous genome-wide association studies have identified over 100 loci for the most common form, primary open-angle glaucoma. Two key glaucoma-associated traits also show high heritability: intraocular pressure and optic nerve head excavation damage quantified as the vertical cup-to-disc ratio. Here, since much of glaucoma heritability remains unexplained, we conducted a large-scale multitrait genome-wide association study in participants of European ancestry combining primary open-angle glaucoma and its two associated traits (total sample size over 600,000) to substantially improve genetic discovery power (263 loci). We further increased our power by then employing a multiancestry approach,

  • Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression - Nature genetics (2020) · Craig JE, Han X, Qassim A, Hassall M, Cooke Bailey JN, Kinzy TG, Khawaja AP, An J, Marshall H, Gharahkhani P, Igo RP, Graham SL, Healey PR, Ong JS, Zhou T, Siggs O, Law MH, Souzeau E, Ridge B, Hysi PG, Burdon KP, Mills RA, Landers J, Ruddle JB, Agar A, Galanopoulos A, White AJR, Willoughby CE, Andrew NH, Best S, Vincent AL, Goldberg I, Radford-Smith G, Martin NG, Montgomery GW, Vitart V, Hoehn R, Wojciechowski R, Jonas JB, Aung T, Pasquale LR, Cree AJ, Sivaprasad S, Vallabh NA, Viswanathan AC, Pasutto F, Haines JL, Klaver CCW, van Duijn CM, Casson RJ, Foster PJ, Khaw PT, Hammond CJ, Mackey DA, Mitchell P, Lotery AJ, Wiggs JL, Hewitt AW, MacGregor S · PubMed 31959993

    ABSTRACT: Glaucoma, a disease characterized by progressive optic nerve degeneration, can be prevented through timely diagnosis and treatment. We characterized optic nerve photographs of 67,040 UK Biobank participants and used a multitrait genetic model to identify risk loci for glaucoma. A novel glaucoma polygenic risk score (PRS) enables effective risk stratification in unselected glaucoma cases, and modifies penetrance of MYOC p.Gln368Ter, the most common glaucoma-associated myocilin variant. In the unselected glaucoma population, individuals in the top PRS decile reach an absolute risk for glaucoma 10 years earlier than the bottom decile, and are at 15-fold increased risk of developing advanced glaucoma (top 10% vs. remaining 90% OR = 4.20). The PRS predicts glaucoma progression in pros

  • Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma - Nature genetics (2019) · Khawaja AP, Cooke Bailey JN, Wareham NJ, Scott RA, Simcoe M, Igo RP, Song YE, Wojciechowski R, Cheng CY, Khaw PT, Pasquale LR, Haines JL, Foster PJ, Wiggs JL, Hammond CJ, Hysi PG · PubMed 29785010

    ABSTRACT: Glaucoma is the leading cause of irreversible blindness globally. Despite its gravity, the disease is frequently undiagnosed in the community. Raised intraocular pressure (IOP) is the most important risk factor for primary open-angle glaucoma (POAG). Here we present a meta-analysis of 139,555 European participants that identified 112 genomic loci associated with IOP, 68 of which are novel. These loci suggest a strong role for angiopoietin-receptor tyrosine kinase signaling, lipid metabolism, mitochondrial function and developmental processes underlying risk for elevated IOP. In addition, 48 of these loci were associated with glaucoma in an independent cohort, 14 of which at a Bonferroni-corrected threshold. Regression-based glaucoma prediction models had an area under Receiving O

  • Genome-wide association study of intraocular pressure uncovers new pathways to glaucoma. - Nature genetics (2019) · MacGregor S, Ong JS, An J, Han X, Zhou T, Siggs OM, Law MH, Souzeau E, Sharma S, Lynn DJ, Beesley J, Sheldrick B, Mills RA, Landers J, Ruddle JB, Graham SL, Healey PR, White AJR, Casson RJ, Best S, Grigg JR, Goldberg I, Powell JE, Whiteman DC, Radford-Smith GL, Martin NG, Montgomery GW, Burdon KP, Mackey DA, Gharahkhani P, Craig JE, Hewitt AW · PubMed 30054594

    Intraocular pressure (IOP) is currently the sole modifiable risk factor for primary open-angle glaucoma (POAG), one of the leading causes of blindness worldwide . Both IOP and POAG are highly heritable . We report a combined analysis of participants from the UK Biobank (n = 103,914) and previously published data from the International Glaucoma Genetic Consortium (n = 29,578) that identified 101 statistically independent genome-wide-significant SNPs for IOP, 85 of which have not been previously reported . We examined these SNPs in 11,018 glaucoma cases and 126,069 controls, and 53 SNPs showed evidence of association. Gene-based tests implicated an additional 22 independent genes associated with IOP. We derived an allele score based on the IOP loci and loci influencing optic nerve he

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