PMID- 28848321
OWN - NLM
STAT- MEDLINE
DCOM- 20180413
LR  - 20221207
IS  - 1090-0535 (Electronic)
IS  - 1090-0535 (Linking)
VI  - 23
DP  - 2017
TI  - Association and interaction of myopia with SNP markers rs13382811 and rs6469937 
      at ZFHX1B and SNTB1 in Han Chinese and European populations.
PG  - 588-604
AB  - PURPOSE: Previously, a genome-wide association study (GWAS) identified rs13382811 
      (near ZFHX1B) and rs6469937 (near SNTB1) to be associated with high myopia. The 
      present study evaluates the association of these two single nucleotide 
      polymorphisms (SNPs) with moderate to high myopia in two Chinese cohorts and two 
      cohorts of European populations. METHODS: Two Chinese university student cohorts, 
      including one with 300 unrelated subjects with high myopia and 308 emmetropic 
      controls from Guangzhou and a second with 96 unrelated individuals with moderate 
      to high myopia and 96 emmetropic controls of Chaoshanese origin in Guangzhou, 
      were enrolled in this study. Two SNPs, rs6469937 and rs13382811, were selected 
      for genotyping based on their reported associations with severe myopia. The SNPs 
      were genotyped via DNA sequencing. In addition, association analysis of both SNPs 
      was performed using genotype data from the database of Genotypes and Phenotypes 
      (dbGaP) involving a total of 2,423 samples in two independent cohorts of 
      European-derived populations, as follows: Kooperative Gesundheitsforschung in der 
      Region Augsburg (KORA) and TwinsUK. The allelic and genotypic distribution among 
      cases and controls were analyzed using the Chi-square test. Logistic regression 
      was used to evaluate the SNP-SNP interaction. Fisher's exact test was used for 
      two-SNP comparisons. RESULTS: In the Guangzhou cohort, SNP rs13382811 near ZFHX1B 
      showed significant association with high myopia (p(allelic) = 0.0001, 
      p(genotypic) = 4.07 x 10(-5)), with the minor T allele showing an increased risk 
      of high myopia (odds ratio [OR] = 1.68, 95% confidence interval [CI] = 
      1.28-2.20). SNP rs6469937 near SNTB1 showed nominal evidence of association 
      (p(allelic) = 0.0085, p(genotypic) = 0.0166), which did not withstand correction 
      for multiple testing. No significant association was detected in the smaller 
      Chaoshan cohort alone. The association of SNPs rs13382811 and rs6469937 remained 
      significant when both Han Chinese cohorts were combined (p(allelic) = 0.0033 and 
      0.0016, respectively), and it was also significant under the genotypic test 
      (p(genotypic) = 0.0036 and 0.0053, respectively). When both SNPs were considered 
      together under a recessive model, their significance increased (p = 8.37 x 
      10(-4)), as did their effect (OR = 4.09, 95%CI = 1.7-9.8). The association 
      between either of these two SNPs alone and myopia did not replicate significantly 
      in the combined cohorts of European descent, providing only suggestive results 
      (p(allelic) = 0.0088 for rs13382811 and p(allelic) = 0.0319 for rs6469937). 
      However, the effects of the combined SNPs showed significant association (p = 8.2 
      x 10(-4); OR = 1.56, 95%CI = 1.2-2.0). While the risk for myopia increased with 
      risk alleles from both SNPs, the increase was additive rather representing a 
      multiplicative interaction in both populations. CONCLUSIONS: Our study confirms 
      that the two susceptibility loci ZFHX1B and SNTB1 are associated with moderate to 
      high myopia in a Han Chinese population, as well as in a European population, 
      when both SNPs are combined. These results confirm previous reports of their 
      associations, extend these observations to a European population, and suggest 
      that additional interactive and possibly population-specific genetic or 
      environmental factors may affect their contribution to myopia.
FAU - Li, Jiali
AU  - Li J
AD  - Ophthalmic Genetics and Visual Function Branch, National Eye Institute, NIH, 
      Bethesda, MD.
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Jiao, Xiaodong
AU  - Jiao X
AD  - Ophthalmic Genetics and Visual Function Branch, National Eye Institute, NIH, 
      Bethesda, MD.
FAU - Zhang, Qingjiong
AU  - Zhang Q
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Hejtmancik, J Fielding
AU  - Hejtmancik JF
AD  - Ophthalmic Genetics and Visual Function Branch, National Eye Institute, NIH, 
      Bethesda, MD.
LA  - eng
PT  - Journal Article
DEP - 20170811
PL  - United States
TA  - Mol Vis
JT  - Molecular vision
JID - 9605351
RN  - 0 (Dystrophin-Associated Proteins)
RN  - 0 (Genetic Markers)
RN  - 0 (ZEB2 protein, human)
RN  - 0 (Zinc Finger E-box Binding Homeobox 2)
RN  - 0 (syntrophin)
SB  - IM
MH  - Alleles
MH  - Asian People/*genetics
MH  - China/epidemiology
MH  - Cohort Studies
MH  - Dystrophin-Associated Proteins/*genetics
MH  - Female
MH  - Genetic Association Studies
MH  - Genetic Markers
MH  - *Genetic Predisposition to Disease
MH  - Genotyping Techniques
MH  - Humans
MH  - Male
MH  - Myopia, Degenerative/*genetics
MH  - Odds Ratio
MH  - *Polymorphism, Single Nucleotide
MH  - Sequence Analysis, DNA
MH  - White People/*genetics
MH  - Young Adult
MH  - Zinc Finger E-box Binding Homeobox 2/*genetics
PMC - PMC5561140
EDAT- 2017/08/30 06:00
MHDA- 2018/04/14 06:00
PMCR- 2017/01/01
CRDT- 2017/08/30 06:00
PHST- 2017/04/04 00:00 [received]
PHST- 2017/08/09 00:00 [accepted]
PHST- 2017/08/30 06:00 [entrez]
PHST- 2017/08/30 06:00 [pubmed]
PHST- 2018/04/14 06:00 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 54 [pii]
PST - epublish
SO  - Mol Vis. 2017 Aug 11;23:588-604. eCollection 2017.