Objective: To investigate the association of high myopia with common single-nucleotide polymorphisms (SNPs) in the IGF1, IGFBP3, and IGFBP4 genes in a Chinese population. Methods: For our case-control study, we recruited 600 unrelated participants: 300 case participants with high myopia (−8.00 diopters or less) and 300 emmetropic controls (within ±1.00 diopter). Twenty-one tag SNPs were selected from these candidate genes and were genotyped. Genotype data were analyzed by logistic regression. Multiple comparisons were corrected by running 15 000 permutations of case-control status. Results: Although we did not find any significant association for IGF1 SNPs using single-marker analysis, we identified many windows with haplotype frequencies significantly different between case participants and control participants using a variable-sized sliding-window strategy. In particular, the most significant association was shown by a 3-SNP window consisting of rs12423791, rs7956547, and rs5742632 (omnibus test: asymptotic P asym =3.70ϫ10 −9 and empirical P emp =6.67ϫ10 −5). There were 3 high-risk haplotypes: CAC (P asym =2.35ϫ10 −6 ; odds ratio [OR], 5.06), GAT (P asym =3.56ϫ10 −4 ; OR, 3.18), and GGC (P asym =2.25ϫ 10 −3 ; OR, 25.10). There was 1 protective haplotype: GAC (P asym =8.43ϫ10 −4 ; OR, 0.63). On the other hand, our single-marker and haplotype analyses did not show any significant association for IGFBP3 and IGFBP4. Conclusions: IGF1 haplotypes are associated with genetic susceptibility to high myopia in Chinese adults, whereas IGFBP3 and IGFBP4 are unlikely to be important in the genetic predisposition to high myopia. Clinical Relevance: IGF1 is associated with high myopia, and identifying the causal variants is important for understanding the underlying mechanisms.

This study demonstrates the association of PAX6 variants with susceptibility to high myopia. The PAX6 locus may contain polymorphisms playing a role in high myopia in southern Han Chinese.