Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations

Pieter W M Bonnemaijer; Adriana I Iglesias; Girish N Nadkarni; Anna J Sanyiwa; Hassan G Hassan; Colin Cook; Mark Simcoe; Kent D Taylor; Claudia Schurmann; Gillian M Belbin; Eimear E Kenny; Erwin P Bottinger; Suzanne van de Laar; Susan E I Wiliams; Stephen K Akafo; Adeyinka O Ashaye; Linda M Zangwill; Christopher A Girkin; Maggie C Y Ng; Jerome I Rotter; Robert N Weinreb; Zheng Li; R Rand Allingham; Abhishek Nag; Pirro G Hysi; Magda A Meester-Smoor; Janey L Wiggs; Michael A Hauser; Christopher J Hammond; Hans G Lemij; Ruth J F Loos; Cornelia M van Duijn; Alberta A H J Thiadens; Caroline C W Klaver

doi:10.1007/s00439-018-1943-7

Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations

, Pieter W M Bonnemaijer, Adriana I Iglesias, Girish N Nadkarni, Anna J Sanyiwa, Hassan G Hassan, Colin Cook, Mark Simcoe, Kent D Taylor, Claudia Schurmann, Gillian M Belbin, Eimear E Kenny, Erwin P Bottinger, Suzanne van de Laar, Susan E I Wiliams, Stephen K Akafo, Adeyinka O Ashaye, Linda M Zangwill, Christopher A Girkin, Maggie C Y NgJerome I Rotter, Robert N Weinreb, Zheng Li, R Rand Allingham, Abhishek Nag, Pirro G Hysi, Magda A Meester-Smoor, Janey L Wiggs, Michael A Hauser, Christopher J Hammond, Hans G Lemij, Ruth J F Loos, Cornelia M van Duijn, Alberta A H J Thiadens, Caroline C W Klaver

Glaucoma

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › Onderzoek › peer review

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Primary open angle glaucoma (POAG) is a complex disease with a major genetic contribution. Its prevalence varies greatly among ethnic groups, and is up to five times more frequent in black African populations compared to Europeans. So far, worldwide efforts to elucidate the genetic complexity of POAG in African populations has been limited. We conducted a genome-wide association study in 1113 POAG cases and 1826 controls from Tanzanian, South African and African American study samples. Apart from confirming evidence of association at TXNRD2 (rs16984299; OR[T] 1.20; P = 0.003), we found that a genetic risk score combining the effects of the 15 previously reported POAG loci was significantly associated with POAG in our samples (OR 1.56; 95% CI 1.26-1.93; P = 4.79 × 10-5). By genome-wide association testing we identified a novel candidate locus, rs141186647, harboring EXOC4 (OR[A] 0.48; P = 3.75 × 10-8), a gene transcribing a component of the exocyst complex involved in vesicle transport. The low frequency and high degree of genetic heterogeneity at this region hampered validation of this finding in predominantly West-African replication sets. Our results suggest that established genetic risk factors play a role in African POAG, however, they do not explain the higher disease load. The high heterogeneity within Africans remains a challenge to identify the genetic commonalities for POAG in this ethnicity, and demands studies of extremely large size.

Originele taal-2	Engels
Pagina's (van-tot)	847-862
Aantal pagina's	16
Tijdschrift	Human Genetics
Volume	137
Nummer van het tijdschrift	10
DOI's	https://doi.org/10.1007/s00439-018-1943-7
Status	Gepubliceerd - okt. 2018

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10.1007/s00439-018-1943-7

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, Bonnemaijer, P. W. M., Iglesias, A. I., Nadkarni, G. N., Sanyiwa, A. J., Hassan, H. G., Cook, C., Simcoe, M., Taylor, K. D., Schurmann, C., Belbin, G. M., Kenny, E. E., Bottinger, E. P., van de Laar, S., Wiliams, S. E. I., Akafo, S. K., Ashaye, A. O., Zangwill, L. M., Girkin, C. A., ... Klaver, C. C. W. (2018). Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations. Human Genetics, 137(10), 847-862. https://doi.org/10.1007/s00439-018-1943-7

@article{cda948bc233c4137bdf15194639b984e,

title = "Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations",

abstract = "Primary open angle glaucoma (POAG) is a complex disease with a major genetic contribution. Its prevalence varies greatly among ethnic groups, and is up to five times more frequent in black African populations compared to Europeans. So far, worldwide efforts to elucidate the genetic complexity of POAG in African populations has been limited. We conducted a genome-wide association study in 1113 POAG cases and 1826 controls from Tanzanian, South African and African American study samples. Apart from confirming evidence of association at TXNRD2 (rs16984299; OR[T] 1.20; P = 0.003), we found that a genetic risk score combining the effects of the 15 previously reported POAG loci was significantly associated with POAG in our samples (OR 1.56; 95% CI 1.26-1.93; P = 4.79 × 10-5). By genome-wide association testing we identified a novel candidate locus, rs141186647, harboring EXOC4 (OR[A] 0.48; P = 3.75 × 10-8), a gene transcribing a component of the exocyst complex involved in vesicle transport. The low frequency and high degree of genetic heterogeneity at this region hampered validation of this finding in predominantly West-African replication sets. Our results suggest that established genetic risk factors play a role in African POAG, however, they do not explain the higher disease load. The high heterogeneity within Africans remains a challenge to identify the genetic commonalities for POAG in this ethnicity, and demands studies of extremely large size.",

keywords = "African Continental Ancestry Group/genetics, Aged, Aged, 80 and over, Female, Genetic Loci, Genome-Wide Association Study, Glaucoma, Open-Angle/genetics, Humans, Male, Middle Aged, Thioredoxin Reductase 2/genetics, Vesicular Transport Proteins/genetics",

author = "Bonnemaijer, {Pieter W M} and Iglesias, {Adriana I} and Nadkarni, {Girish N} and Sanyiwa, {Anna J} and Hassan, {Hassan G} and Colin Cook and Mark Simcoe and Taylor, {Kent D} and Claudia Schurmann and Belbin, {Gillian M} and Kenny, {Eimear E} and Bottinger, {Erwin P} and {van de Laar}, Suzanne and Wiliams, {Susan E I} and Akafo, {Stephen K} and Ashaye, {Adeyinka O} and Zangwill, {Linda M} and Girkin, {Christopher A} and Ng, {Maggie C Y} and Rotter, {Jerome I} and Weinreb, {Robert N} and Zheng Li and Allingham, {R Rand} and Abhishek Nag and Hysi, {Pirro G} and Meester-Smoor, {Magda A} and Wiggs, {Janey L} and Hauser, {Michael A} and Hammond, {Christopher J} and Lemij, {Hans G} and Loos, {Ruth J F} and {van Duijn}, {Cornelia M} and Thiadens, {Alberta A H J} and Klaver, {Caroline C W}",

year = "2018",

month = oct,

doi = "10.1007/s00439-018-1943-7",

language = "English",

volume = "137",

pages = "847--862",

number = "10",

}

Bonnemaijer, PWM, Iglesias, AI, Nadkarni, GN, Sanyiwa, AJ, Hassan, HG, Cook, C, Simcoe, M, Taylor, KD, Schurmann, C, Belbin, GM, Kenny, EE, Bottinger, EP, van de Laar, S, Wiliams, SEI, Akafo, SK, Ashaye, AO, Zangwill, LM, Girkin, CA, Ng, MCY, Rotter, JI, Weinreb, RN, Li, Z, Allingham, RR, Nag, A, Hysi, PG, Meester-Smoor, MA, Wiggs, JL, Hauser, MA, Hammond, CJ, Lemij, HG, Loos, RJF, van Duijn, CM & Thiadens, AAHJ & Klaver, CCW 2018, 'Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations', Human Genetics, vol. 137, nr. 10, blz. 847-862. https://doi.org/10.1007/s00439-018-1943-7

TY - JOUR

T1 - Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations

AU - Bonnemaijer, Pieter W M

AU - Iglesias, Adriana I

AU - Nadkarni, Girish N

AU - Sanyiwa, Anna J

AU - Hassan, Hassan G

AU - Cook, Colin

AU - Simcoe, Mark

AU - Taylor, Kent D

AU - Schurmann, Claudia

AU - Belbin, Gillian M

AU - Kenny, Eimear E

AU - Bottinger, Erwin P

AU - van de Laar, Suzanne

AU - Wiliams, Susan E I

AU - Akafo, Stephen K

AU - Ashaye, Adeyinka O

AU - Zangwill, Linda M

AU - Girkin, Christopher A

AU - Ng, Maggie C Y

AU - Rotter, Jerome I

AU - Weinreb, Robert N

AU - Li, Zheng

AU - Allingham, R Rand

AU - Nag, Abhishek

AU - Hysi, Pirro G

AU - Meester-Smoor, Magda A

AU - Wiggs, Janey L

AU - Hauser, Michael A

AU - Hammond, Christopher J

AU - Lemij, Hans G

AU - Loos, Ruth J F

AU - van Duijn, Cornelia M

AU - Thiadens, Alberta A H J

AU - Klaver, Caroline C W

PY - 2018/10

Y1 - 2018/10

N2 - Primary open angle glaucoma (POAG) is a complex disease with a major genetic contribution. Its prevalence varies greatly among ethnic groups, and is up to five times more frequent in black African populations compared to Europeans. So far, worldwide efforts to elucidate the genetic complexity of POAG in African populations has been limited. We conducted a genome-wide association study in 1113 POAG cases and 1826 controls from Tanzanian, South African and African American study samples. Apart from confirming evidence of association at TXNRD2 (rs16984299; OR[T] 1.20; P = 0.003), we found that a genetic risk score combining the effects of the 15 previously reported POAG loci was significantly associated with POAG in our samples (OR 1.56; 95% CI 1.26-1.93; P = 4.79 × 10-5). By genome-wide association testing we identified a novel candidate locus, rs141186647, harboring EXOC4 (OR[A] 0.48; P = 3.75 × 10-8), a gene transcribing a component of the exocyst complex involved in vesicle transport. The low frequency and high degree of genetic heterogeneity at this region hampered validation of this finding in predominantly West-African replication sets. Our results suggest that established genetic risk factors play a role in African POAG, however, they do not explain the higher disease load. The high heterogeneity within Africans remains a challenge to identify the genetic commonalities for POAG in this ethnicity, and demands studies of extremely large size.

AB - Primary open angle glaucoma (POAG) is a complex disease with a major genetic contribution. Its prevalence varies greatly among ethnic groups, and is up to five times more frequent in black African populations compared to Europeans. So far, worldwide efforts to elucidate the genetic complexity of POAG in African populations has been limited. We conducted a genome-wide association study in 1113 POAG cases and 1826 controls from Tanzanian, South African and African American study samples. Apart from confirming evidence of association at TXNRD2 (rs16984299; OR[T] 1.20; P = 0.003), we found that a genetic risk score combining the effects of the 15 previously reported POAG loci was significantly associated with POAG in our samples (OR 1.56; 95% CI 1.26-1.93; P = 4.79 × 10-5). By genome-wide association testing we identified a novel candidate locus, rs141186647, harboring EXOC4 (OR[A] 0.48; P = 3.75 × 10-8), a gene transcribing a component of the exocyst complex involved in vesicle transport. The low frequency and high degree of genetic heterogeneity at this region hampered validation of this finding in predominantly West-African replication sets. Our results suggest that established genetic risk factors play a role in African POAG, however, they do not explain the higher disease load. The high heterogeneity within Africans remains a challenge to identify the genetic commonalities for POAG in this ethnicity, and demands studies of extremely large size.

KW - African Continental Ancestry Group/genetics

KW - Aged

KW - Aged, 80 and over

KW - Female

KW - Genetic Loci

KW - Genome-Wide Association Study

KW - Glaucoma, Open-Angle/genetics

KW - Humans

KW - Male

KW - Middle Aged

KW - Thioredoxin Reductase 2/genetics

KW - Vesicular Transport Proteins/genetics

U2 - 10.1007/s00439-018-1943-7

DO - 10.1007/s00439-018-1943-7

M3 - Article

C2 - 30317457

SN - 1432-1203

VL - 137

SP - 847

EP - 862

JO - Human Genetics

JF - Human Genetics

IS - 10

ER -

Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations

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