Investigation of known genetic risk factors for primary open angle glaucoma in two populations of African ancestry

Yutao Liu, Michael A. Hauser, Stephen K. Akafo, Xuejun Qin, Shiroh Miura, Jason R. Gibson, Joshua Wheeler, Douglas E. Gaasterland, Pratap Challa, Leon W. Herndon, Robert Ritch, Sayoko E. Moroi, Louis R. Pasquale, Christopher A. Girkin, Donald L. Budenz, Janey L. Wiggs, Julia E. Richards, Allison E. Ashley-Koch, R. Rand Allingham

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Purpose. Multiple genes have been associated with primary open angle glaucoma (POAG) in Caucasian populations. We now examine the association of these loci in populations of African ancestry, populations at particularly high risk for POAG. Methods. We genotyped DNA samples from two populations: African American (1150 cases and 999 controls) and those from Ghana, West Africa (483 cases and 593 controls). Our analysis included 57 single nucleotide polymorphisms (SNPs) in five loci previously associated with POAG at the genome-wide level, including CDKN2B-AS1, TMCO1, CAV1/CAV2, chromosome 8q22 intergenic region, and SIX1/SIX6. We evaluated association in the full datasets, as well as subgroups with normal pressure glaucoma (NPG, maximum IOP ≤21 mm Hg) and high pressure glaucoma (HPG, IOP >21 mm Hg). Results. In African Americans, we identified an association of rs10120688 in the CDNK2B-AS1 region with POAG (P = 0.0020). Several other SNPs were nominally associated, but did not survive correction for multiple testing. In the subgroup analyses, significant associations were identified for rs10965245 (P = 0.0005) in the CDKN2B-AS1 region with HPG and rs11849906 in the SIX1/SIX6 region with NPG (P = 0.006). No significant association was identified with any loci in the Ghanaian samples. Conclusions. POAG genetic susceptibility alleles associated in Caucasians appear to play a greatly reduced role in populations of African ancestry. Thus, the major genetic components of POAG of African origin remain to be identified. This finding underscores the critical need to pursue large-scale genome-wide association studies in this understudied, yet disproportionately affected population.

Original languageEnglish (US)
Pages (from-to)6248-6254
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume54
Issue number9
DOIs
StatePublished - Sep 23 2013

Fingerprint

Population
African Americans
Glaucoma
Single Nucleotide Polymorphism
Pressure
Ghana
Intergenic DNA
Western Africa
Genome-Wide Association Study
Genetic Predisposition to Disease
Primary Open Angle Glaucoma
Chromosomes
Alleles
Genome
DNA
Genes
Datasets

Keywords

  • African
  • African American
  • Association
  • Genetics
  • POAG

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Investigation of known genetic risk factors for primary open angle glaucoma in two populations of African ancestry. / Liu, Yutao; Hauser, Michael A.; Akafo, Stephen K.; Qin, Xuejun; Miura, Shiroh; Gibson, Jason R.; Wheeler, Joshua; Gaasterland, Douglas E.; Challa, Pratap; Herndon, Leon W.; Ritch, Robert; Moroi, Sayoko E.; Pasquale, Louis R.; Girkin, Christopher A.; Budenz, Donald L.; Wiggs, Janey L.; Richards, Julia E.; Ashley-Koch, Allison E.; Allingham, R. Rand.

In: Investigative Ophthalmology and Visual Science, Vol. 54, No. 9, 23.09.2013, p. 6248-6254.

Research output: Contribution to journalArticle

Liu, Y, Hauser, MA, Akafo, SK, Qin, X, Miura, S, Gibson, JR, Wheeler, J, Gaasterland, DE, Challa, P, Herndon, LW, Ritch, R, Moroi, SE, Pasquale, LR, Girkin, CA, Budenz, DL, Wiggs, JL, Richards, JE, Ashley-Koch, AE & Allingham, RR 2013, 'Investigation of known genetic risk factors for primary open angle glaucoma in two populations of African ancestry', Investigative Ophthalmology and Visual Science, vol. 54, no. 9, pp. 6248-6254. https://doi.org/10.1167/iovs.13-12779
Liu, Yutao ; Hauser, Michael A. ; Akafo, Stephen K. ; Qin, Xuejun ; Miura, Shiroh ; Gibson, Jason R. ; Wheeler, Joshua ; Gaasterland, Douglas E. ; Challa, Pratap ; Herndon, Leon W. ; Ritch, Robert ; Moroi, Sayoko E. ; Pasquale, Louis R. ; Girkin, Christopher A. ; Budenz, Donald L. ; Wiggs, Janey L. ; Richards, Julia E. ; Ashley-Koch, Allison E. ; Allingham, R. Rand. / Investigation of known genetic risk factors for primary open angle glaucoma in two populations of African ancestry. In: Investigative Ophthalmology and Visual Science. 2013 ; Vol. 54, No. 9. pp. 6248-6254.
@article{84144748308b427b98dc1952097e68ba,
title = "Investigation of known genetic risk factors for primary open angle glaucoma in two populations of African ancestry",
abstract = "Purpose. Multiple genes have been associated with primary open angle glaucoma (POAG) in Caucasian populations. We now examine the association of these loci in populations of African ancestry, populations at particularly high risk for POAG. Methods. We genotyped DNA samples from two populations: African American (1150 cases and 999 controls) and those from Ghana, West Africa (483 cases and 593 controls). Our analysis included 57 single nucleotide polymorphisms (SNPs) in five loci previously associated with POAG at the genome-wide level, including CDKN2B-AS1, TMCO1, CAV1/CAV2, chromosome 8q22 intergenic region, and SIX1/SIX6. We evaluated association in the full datasets, as well as subgroups with normal pressure glaucoma (NPG, maximum IOP ≤21 mm Hg) and high pressure glaucoma (HPG, IOP >21 mm Hg). Results. In African Americans, we identified an association of rs10120688 in the CDNK2B-AS1 region with POAG (P = 0.0020). Several other SNPs were nominally associated, but did not survive correction for multiple testing. In the subgroup analyses, significant associations were identified for rs10965245 (P = 0.0005) in the CDKN2B-AS1 region with HPG and rs11849906 in the SIX1/SIX6 region with NPG (P = 0.006). No significant association was identified with any loci in the Ghanaian samples. Conclusions. POAG genetic susceptibility alleles associated in Caucasians appear to play a greatly reduced role in populations of African ancestry. Thus, the major genetic components of POAG of African origin remain to be identified. This finding underscores the critical need to pursue large-scale genome-wide association studies in this understudied, yet disproportionately affected population.",
keywords = "African, African American, Association, Genetics, POAG",
author = "Yutao Liu and Hauser, {Michael A.} and Akafo, {Stephen K.} and Xuejun Qin and Shiroh Miura and Gibson, {Jason R.} and Joshua Wheeler and Gaasterland, {Douglas E.} and Pratap Challa and Herndon, {Leon W.} and Robert Ritch and Moroi, {Sayoko E.} and Pasquale, {Louis R.} and Girkin, {Christopher A.} and Budenz, {Donald L.} and Wiggs, {Janey L.} and Richards, {Julia E.} and Ashley-Koch, {Allison E.} and Allingham, {R. Rand}",
year = "2013",
month = "9",
day = "23",
doi = "10.1167/iovs.13-12779",
language = "English (US)",
volume = "54",
pages = "6248--6254",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "9",

}

TY - JOUR

T1 - Investigation of known genetic risk factors for primary open angle glaucoma in two populations of African ancestry

AU - Liu, Yutao

AU - Hauser, Michael A.

AU - Akafo, Stephen K.

AU - Qin, Xuejun

AU - Miura, Shiroh

AU - Gibson, Jason R.

AU - Wheeler, Joshua

AU - Gaasterland, Douglas E.

AU - Challa, Pratap

AU - Herndon, Leon W.

AU - Ritch, Robert

AU - Moroi, Sayoko E.

AU - Pasquale, Louis R.

AU - Girkin, Christopher A.

AU - Budenz, Donald L.

AU - Wiggs, Janey L.

AU - Richards, Julia E.

AU - Ashley-Koch, Allison E.

AU - Allingham, R. Rand

PY - 2013/9/23

Y1 - 2013/9/23

N2 - Purpose. Multiple genes have been associated with primary open angle glaucoma (POAG) in Caucasian populations. We now examine the association of these loci in populations of African ancestry, populations at particularly high risk for POAG. Methods. We genotyped DNA samples from two populations: African American (1150 cases and 999 controls) and those from Ghana, West Africa (483 cases and 593 controls). Our analysis included 57 single nucleotide polymorphisms (SNPs) in five loci previously associated with POAG at the genome-wide level, including CDKN2B-AS1, TMCO1, CAV1/CAV2, chromosome 8q22 intergenic region, and SIX1/SIX6. We evaluated association in the full datasets, as well as subgroups with normal pressure glaucoma (NPG, maximum IOP ≤21 mm Hg) and high pressure glaucoma (HPG, IOP >21 mm Hg). Results. In African Americans, we identified an association of rs10120688 in the CDNK2B-AS1 region with POAG (P = 0.0020). Several other SNPs were nominally associated, but did not survive correction for multiple testing. In the subgroup analyses, significant associations were identified for rs10965245 (P = 0.0005) in the CDKN2B-AS1 region with HPG and rs11849906 in the SIX1/SIX6 region with NPG (P = 0.006). No significant association was identified with any loci in the Ghanaian samples. Conclusions. POAG genetic susceptibility alleles associated in Caucasians appear to play a greatly reduced role in populations of African ancestry. Thus, the major genetic components of POAG of African origin remain to be identified. This finding underscores the critical need to pursue large-scale genome-wide association studies in this understudied, yet disproportionately affected population.

AB - Purpose. Multiple genes have been associated with primary open angle glaucoma (POAG) in Caucasian populations. We now examine the association of these loci in populations of African ancestry, populations at particularly high risk for POAG. Methods. We genotyped DNA samples from two populations: African American (1150 cases and 999 controls) and those from Ghana, West Africa (483 cases and 593 controls). Our analysis included 57 single nucleotide polymorphisms (SNPs) in five loci previously associated with POAG at the genome-wide level, including CDKN2B-AS1, TMCO1, CAV1/CAV2, chromosome 8q22 intergenic region, and SIX1/SIX6. We evaluated association in the full datasets, as well as subgroups with normal pressure glaucoma (NPG, maximum IOP ≤21 mm Hg) and high pressure glaucoma (HPG, IOP >21 mm Hg). Results. In African Americans, we identified an association of rs10120688 in the CDNK2B-AS1 region with POAG (P = 0.0020). Several other SNPs were nominally associated, but did not survive correction for multiple testing. In the subgroup analyses, significant associations were identified for rs10965245 (P = 0.0005) in the CDKN2B-AS1 region with HPG and rs11849906 in the SIX1/SIX6 region with NPG (P = 0.006). No significant association was identified with any loci in the Ghanaian samples. Conclusions. POAG genetic susceptibility alleles associated in Caucasians appear to play a greatly reduced role in populations of African ancestry. Thus, the major genetic components of POAG of African origin remain to be identified. This finding underscores the critical need to pursue large-scale genome-wide association studies in this understudied, yet disproportionately affected population.

KW - African

KW - African American

KW - Association

KW - Genetics

KW - POAG

UR - http://www.scopus.com/inward/record.url?scp=84884246440&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84884246440&partnerID=8YFLogxK

U2 - 10.1167/iovs.13-12779

DO - 10.1167/iovs.13-12779

M3 - Article

C2 - 23963167

AN - SCOPUS:84884246440

VL - 54

SP - 6248

EP - 6254

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 9

ER -