title: Quantitative Trait Locus Analysis of SIX1-SIX6 With Retinal Nerve Fiber Layer Thickness in Individuals of European Descent.
abstract: OBJECTIVE
  To perform a quantitative trait locus (QTL) analysis and evaluate whether a locus between SIX1 and SIX6 is associated with retinal nerve fiber layer (RNFL) thickness in individuals of European descent.
  
  
  METHODS
  Observational, multicenter, cross-sectional study.
  
  
  METHODS
  A total of 231 participants were recruited from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. Association of rs10483727 in SIX1-SIX6 with global and sectoral RNFL thickness was performed. Quantitative trait analysis with the additive model of inheritance was analyzed using linear regression. Trend analysis was performed to evaluate the mean global and sectoral RNFL thickness with 3 genotypes of interest (T/T, C/T, C/C). All models were adjusted for age and sex.
  
  
  RESULTS
  Direction of association between T allele and RNFL thickness was consistent in the global and different sectoral RNFL regions. Each copy of the T risk allele in rs10483727 was associated with -0.16 μm thinner global RNFL thickness (β = -0.16, 95% confidence interval: -0.28 to -0.03; P = .01). Similar patterns were found for the sectoral regions, including inferior (P = .03), inferior-nasal (P = .017), superior-nasal (P = .0025), superior (P = .002) and superior-temporal (P = .008). The greatest differences were observed in the superior and inferior quadrants, supporting clinical observations for RNFL thinning in glaucoma. Thinner global RNFL was found in subjects with T/T genotypes compared to subjects with C/T and C/C genotypes (P = .044).
  
  
  CONCLUSIONS
  Each copy of the T risk allele has an additive effect and was associated with thinner global and sectoral RNFL. Findings from this QTL analysis further support a genetic contribution to glaucoma pathophysiology.
authors: Hamilton Glaucoma Center and Department of Ophthalmology, Shiley Eye Institute, University of California San Diego, La Jolla, California; Pathway Genomics Corporation, San Diego, California.
authors: Jane Z
authors: JZ
authors: Kuo
authors: Hamilton Glaucoma Center and Department of Ophthalmology, Shiley Eye Institute, University of California San Diego, La Jolla, California.
authors: Linda M
authors: LM
authors: Zangwill
authors: Hamilton Glaucoma Center and Department of Ophthalmology, Shiley Eye Institute, University of California San Diego, La Jolla, California.
authors: Felipe A
authors: FA
authors: Medeiros
authors: Harkness Eye Institute, Columbia University Medical Center, New York, New York.
authors: Jeffery M
authors: JM
authors: Liebmann
authors: Department of Ophthalmology, University of Alabama, Callahan Eye Hospital, Birmingham, Alabama.
authors: Christopher A
authors: CA
authors: Girkin
authors: Hamilton Glaucoma Center and Department of Ophthalmology, Shiley Eye Institute, University of California San Diego, La Jolla, California.
authors: Na'ama
authors: N
authors: Hammel
authors: Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-University of California Los Angeles Medical Center, Torrance, California.
authors: Jerome I
authors: JI
authors: Rotter
authors: Hamilton Glaucoma Center and Department of Ophthalmology, Shiley Eye Institute, University of California San Diego, La Jolla, California. Electronic address: rweinreb@ucsd.edu.
authors: Robert N
authors: RN
authors: Weinreb
mesh_terms: D000368:Aged; D003430:Cross-Sectional Studies; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D060005:Genotyping Techniques; D005902:Glaucoma, Open-Angle / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012165:Retinal Ganglion Cells / Q000473:pathology*; D015534:Trans-Activators / Q000235:genetics; D044465:White People; D000097607:Homeobox Protein SIX3
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D015534:Trans-Activators; D000097607:Homeobox Protein SIX3; C099236:SIX1 protein, human; C484762:SIX2 protein, human; C490851:SIX4 protein, human; C106687:SIX5 protein, human; C491945:SIX6 protein, human