Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

Pieter W M Bonnemaijer; Elisabeth M V van Leeuwen; Adriana I Iglesias; Puya Gharahkhani; Veronique Vitart; Anthony P Khawaja; Mark Simcoe; René Höhn; Angela J Cree; Rob P Igo; Aslihan Gerhold-Ay; Stefan Nickels; James F Wilson; Caroline Hayward; Thibaud S Boutin; Ozren Polašek; Tin Aung; Chiea Chuen Khor; Najaf Amin; Andrew J Lotery; Janey L Wiggs; Ching-Yu Cheng; Pirro G Hysi; Christopher J Hammond; Alberta A H J Thiadens; Stuart MacGregor; Caroline C W Klaver; Cornelia M van Duijn

doi:10.1038/s42003-019-0634-9

Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

Pieter W M Bonnemaijer, Elisabeth M V van Leeuwen, Adriana I Iglesias, Puya Gharahkhani, Veronique Vitart, Anthony P Khawaja, Mark Simcoe, René Höhn, Angela J Cree, Rob P Igo, , Aslihan Gerhold-Ay, Stefan Nickels, James F Wilson, Caroline Hayward, Thibaud S Boutin, Ozren Polašek, Tin Aung, Chiea Chuen Khor, Najaf AminAndrew J Lotery, Janey L Wiggs, Ching-Yu Cheng, Pirro G Hysi, Christopher J Hammond, Alberta A H J Thiadens, Stuart MacGregor, Caroline C W Klaver, Cornelia M van Duijn

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A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH.

Originele taal-2	Engels
Pagina's (van-tot)	435
Tijdschrift	Communications Biology
Volume	2
DOI's	https://doi.org/10.1038/s42003-019-0634-9
Status	Gepubliceerd - 2019

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10.1038/s42003-019-0634-9Licentie: CC BY

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Bonnemaijer, P. W. M., van Leeuwen, E. M. V., Iglesias, A. I., Gharahkhani, P., Vitart, V., Khawaja, A. P., Simcoe, M., Höhn, R., Cree, A. J., Igo, R. P., Gerhold-Ay, A., Nickels, S., Wilson, J. F., Hayward, C., Boutin, T. S., Polašek, O., Aung, T., Khor, C. C., ... Duijn, C. M. V. (2019). Multi-trait genome-wide association study identifies new loci associated with optic disc parameters. Communications Biology, 2, 435. https://doi.org/10.1038/s42003-019-0634-9

@article{316d7c68854f4e91a686f173e1f6f9df,

title = "Multi-trait genome-wide association study identifies new loci associated with optic disc parameters",

abstract = "A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH.",

author = "Bonnemaijer, \{Pieter W M\} and \{van Leeuwen\}, \{Elisabeth M V\} and Iglesias, \{Adriana I\} and Puya Gharahkhani and Veronique Vitart and Khawaja, \{Anthony P\} and Mark Simcoe and Ren{\'e} H{\"o}hn and Cree, \{Angela J\} and Igo, \{Rob P\} and Aslihan Gerhold-Ay and Stefan Nickels and Wilson, \{James F\} and Caroline Hayward and Boutin, \{Thibaud S\} and Ozren Pola{\v s}ek and Tin Aung and Khor, \{Chiea Chuen\} and Najaf Amin and Lotery, \{Andrew J\} and Wiggs, \{Janey L\} and Ching-Yu Cheng and Hysi, \{Pirro G\} and Hammond, \{Christopher J\} and Thiadens, \{Alberta A H J\} and Stuart MacGregor and Klaver, \{Caroline C W\} and Duijn, \{Cornelia M van\}",

note = "{\textcopyright} The Author(s) 2019.",

year = "2019",

doi = "10.1038/s42003-019-0634-9",

language = "English",

volume = "2",

pages = "435",

}

Bonnemaijer, PWM, van Leeuwen, EMV, Iglesias, AI, Gharahkhani, P, Vitart, V, Khawaja, AP, Simcoe, M, Höhn, R, Cree, AJ, Igo, RP, Gerhold-Ay, A, Nickels, S, Wilson, JF, Hayward, C, Boutin, TS, Polašek, O, Aung, T, Khor, CC, Amin, N, Lotery, AJ, Wiggs, JL, Cheng, C-Y, Hysi, PG, Hammond, CJ, Thiadens, AAHJ, MacGregor, S & Klaver, CCW & Duijn, CMV 2019, 'Multi-trait genome-wide association study identifies new loci associated with optic disc parameters', Communications Biology, vol. 2, blz. 435. https://doi.org/10.1038/s42003-019-0634-9

TY - JOUR

T1 - Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

AU - Bonnemaijer, Pieter W M

AU - van Leeuwen, Elisabeth M V

AU - Iglesias, Adriana I

AU - Gharahkhani, Puya

AU - Vitart, Veronique

AU - Khawaja, Anthony P

AU - Simcoe, Mark

AU - Höhn, René

AU - Cree, Angela J

AU - Igo, Rob P

AU - Gerhold-Ay, Aslihan

AU - Nickels, Stefan

AU - Wilson, James F

AU - Hayward, Caroline

AU - Boutin, Thibaud S

AU - Polašek, Ozren

AU - Aung, Tin

AU - Khor, Chiea Chuen

AU - Amin, Najaf

AU - Lotery, Andrew J

AU - Wiggs, Janey L

AU - Cheng, Ching-Yu

AU - Hysi, Pirro G

AU - Hammond, Christopher J

AU - Thiadens, Alberta A H J

AU - MacGregor, Stuart

AU - Klaver, Caroline C W

AU - Duijn, Cornelia M van

PY - 2019

Y1 - 2019

N2 - A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH.

AB - A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH.

U2 - 10.1038/s42003-019-0634-9

DO - 10.1038/s42003-019-0634-9

M3 - Article

C2 - 31798171

SN - 2399-3642

VL - 2

SP - 435

JO - Communications Biology

JF - Communications Biology

ER -

Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

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