title: Linkage and association analyses of glaucoma related traits in a large pedigree from a Dutch genetically isolated population.
abstract: BACKGROUND
  Despite extensive research on the genetic determinants of glaucoma, the genes identified to date explain only a small proportion of cases in the general population.
  
  
  METHODS
  Genome-wide linkage and association analyses of quantitative traits related to glaucoma were performed: intraocular pressure, size and morphology of the optic disc (individual and combined by method of principal components) and thickness of the retinal nerve fibre layer (RNFL), in a large pedigree from a genetically isolated Dutch population.
  
  
  RESULTS
  For the size of the optic disc, the study demonstrated a significant linkage signal (logarithm of odds (LOD)=3.6) at the LRP1B region on chromosome 2q21.2-q22.2 and significant association (p=8.95×10(-12)) with the previously reported CDC7/TGFBR3 locus at 1p22. For parameters describing morphology of the optic disc, the study obtained significant linkage signal (LOD=4.6) at regions SIRPA and RNF24/PANK2 at 20p13 (false discovery rate (FDR) based q value <0.05) and genome-wide significant association (p=2.38×10(-9)) with a common variant in the RERE gene at 1p36. Suggestive linkage and association signals indicated loci for morphology of the optic disc at 2q31-q33 (IGFBP2 locus) and for RNFL thickness at 3p22.2 (DCLK3 locus) and 14q22-q23 (SIX1 locus).
  
  
  CONCLUSIONS
  This study identified new linkage regions at 20p13 (SIRPA and RNF24/PANK2 loci) and 2q33-q34 (IGFBP2 locus) for parameters describing morphology of the optic disc. The results of the study also suggested common genetic control of these parameters and RNFL thickness by SIX1 and doublecotin family genes. Finally, association signals for the recently reported RERE and LRP1B loci and the well known CDC7, TGFBR3, and ATOH7 loci were replicated.
authors: Institute of Cytology & Genetics, Lavrentiev Avenue 10, Novosibirsk 630090, Russian Federation. aks@bionet.nsc.ru
authors: Tatiana
authors: T
authors: Axenovich
authors: Irina
authors: I
authors: Zorkoltseva
authors: Nadezhda
authors: N
authors: Belonogova
authors: Leonike M E
authors: LM
authors: van Koolwijk
authors: Leonike
authors: L
authors: van Koolwijk
authors: Pavel
authors: P
authors: Borodin
authors: Anatoly
authors: A
authors: Kirichenko
authors: Vladimir
authors: V
authors: Babenko
authors: Wishal D
authors: WD
authors: Ramdas
authors: Wishal
authors: W
authors: Ramdas
authors: Najaf
authors: N
authors: Amin
authors: Dominiec D G
authors: DD
authors: Despriet
authors: Dominiec
authors: D
authors: Despriet
authors: Johannes R
authors: JR
authors: Vingerling
authors: Johannes
authors: J
authors: Vingerling
authors: Hans G
authors: HG
authors: Lemij
authors: Hans
authors: H
authors: Lemij
authors: B A
authors: BA
authors: Oostra
authors: Caroline C W
authors: CC
authors: Klaver
authors: Caroline
authors: C
authors: Klaver
authors: Yurii   S
authors: Y
authors: Aulchenko
authors: Yurii
authors: Y
authors: Aulchenko
authors: Cornelia M
authors: CM
authors: van Duijn
authors: Cornelia
authors: C
authors: van Duijn
mesh_terms: D000943:Antigens, Differentiation / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002877:Chromosomes, Human / Q000235:genetics; D008040:Genetic Linkage; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D005901:Glaucoma / Q000235:genetics* / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics; D007429:Intraocular Pressure / Q000235:genetics; D009426:Netherlands; D009898:Optic Disk / Q000166:cytology / Q000473:pathology; D010375:Pedigree; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D019655:Quantitative Trait, Heritable; D011971:Receptors, Immunologic / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics; D012160:Retina / Q000166:cytology / Q000473:pathology
chemical_list: D000943:Antigens, Differentiation; D002352:Carrier Proteins; D018398:Homeodomain Proteins; D018971:Insulin-Like Growth Factor Binding Protein 2; C434476:LRP1B protein, human; C412477:RERE protein, human; D011971:Receptors, Immunologic; D011973:Receptors, LDL; C501920:SIRPA protein, human; C099236:SIX1 protein, human; D017853:Phosphotransferases (Alcohol Group Acceptor); C023088:pantothenate kinase