title: Investigation of known genetic risk factors for primary open angle glaucoma in two populations of African ancestry.
abstract: OBJECTIVE
  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.
authors: Department of Medicine, Duke University Medical Center, Durham, North Carolina.
authors: Yutao
authors: Y
authors: Liu
authors: Michael A
authors: MA
authors: Hauser
authors: Stephen K
authors: SK
authors: Akafo
authors: Xuejun
authors: X
authors: Qin
authors: Shiroh
authors: S
authors: Miura
authors: Jason R
authors: JR
authors: Gibson
authors: Joshua
authors: J
authors: Wheeler
authors: Douglas E
authors: DE
authors: Gaasterland
authors: Pratap
authors: P
authors: Challa
authors: Leon W
authors: LW
authors: Herndon
authors: Robert
authors: R
authors: Ritch
authors: Sayoko E
authors: SE
authors: Moroi
authors: Louis R
authors: LR
authors: Pasquale
authors: Christopher A
authors: CA
authors: Girkin
authors: Donald L
authors: DL
authors: Budenz
authors: Janey L
authors: JL
authors: Wiggs
authors: Julia E
authors: JE
authors: Richards
authors: Allison E
authors: AE
authors: Ashley-Koch
authors: R Rand
authors: RR
authors: Allingham
mesh_terms: D000368:Aged; D044383:Black People / Q000235:genetics*; D015220:Calcium Channels; D051242:Caveolin 1 / Q000235:genetics; D051243:Caveolin 2 / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005902:Glaucoma, Open-Angle / Q000208:ethnology / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D062085:RNA, Long Noncoding / Q000235:genetics; D012307:Risk Factors; D015534:Trans-Activators / Q000235:genetics; D001741:Black or African American
chemical_list: C495540:CAV1 protein, human; C495544:CAV2 protein, human; C561518:CDKN2B antisense RNA, human; D015220:Calcium Channels; D051242:Caveolin 1; D051243:Caveolin 2; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D062085:RNA, Long Noncoding; C099236:SIX1 protein, human; C491945:SIX6 protein, human; C575495:TMCO1 protein, human; D015534:Trans-Activators
keywords: African; African American; POAG; association; genetics
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