Association of <emph type="ital">IGF1</emph> Gene Haplotypes With High Myopia in Chinese Adults

Abstract

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.

Association of High Myopia with Crystallin Beta A4 (CRYBA4) Gene Polymorphisms in the Linkage-Identified MYP6 Locus

“…This variation in the LD measures give rise to different boundaries between two LD blocks (Blocks 2 and 3; Figure 1) for these two Chinese populations. This fine-scale variation in LD patterns is not uncommon because LD is influenced by population histories among other things, as has also been observed in some of our previous studies [24]–[26].…”

Association of High Myopia with Crystallin Beta A4 (CRYBA4) Gene Polymorphisms in the Linkage-Identified MYP6 Locus

“…This variation in the LD measures give rise to different boundaries between two LD blocks (Blocks 2 and 3; Figure 1) for these two Chinese populations. This fine-scale variation in LD patterns is not uncommon because LD is influenced by population histories among other things, as has also been observed in some of our previous studies [24]–[26].…”

The G allele of the IGF1 rs2162679 SNP is a potential protective factor for any myopia: Updated systematic review and meta-analysis

“…Among these SNPs, seven were tested in at least three studies and then were included in the meta-analysis. The study subjects were Chinese [ 29 , 31 , 32 , 34 , 35 ], Japanese [ 27 , 28 ], Egyptian [ 33 ] and Polish [ 30 ] with sample sizes that ranged from 127 to 1339. The total sample size was 9546 (4596 individuals with any myopia and 4950 controls).…”

“…Rs12423791 was tested in six studies [ 27 – 29 , 31 , 32 , 35 ] with 2971 cases and 3150 controls. Random-effects models were used to calculate the pooled ORs.…”

Genetic association between germline JAK2polymorphisms and myeloproliferative neoplasms in Hong Kong Chinese population: a case–control study

“…Multiple comparisons were corrected by 50,000 permutations to give the P emp value. e These three SNPs (S8, S9 and S13) were directly genotyped in this study while the rest were imputed by Beagle v3.2 [ 41 ].…”

Association of High Myopia with Crystallin Beta A4 (CRYBA4) Gene Polymorphisms in the Linkage-Identified MYP6 Locus

“…This variation in the LD measures give rise to different boundaries between two LD blocks (Blocks 2 and 3; Figure 1) for these two Chinese populations. This fine-scale variation in LD patterns is not uncommon because LD is influenced by population histories among other things, as has also been observed in some of our previous studies [24]–[26].…”

The G allele of the IGF1 rs2162679 SNP is a potential protective factor for any myopia: Updated systematic review and meta-analysis

“…Among these SNPs, seven were tested in at least three studies and then were included in the meta-analysis. The study subjects were Chinese [ 29 , 31 , 32 , 34 , 35 ], Japanese [ 27 , 28 ], Egyptian [ 33 ] and Polish [ 30 ] with sample sizes that ranged from 127 to 1339. The total sample size was 9546 (4596 individuals with any myopia and 4950 controls).…”

“…Rs12423791 was tested in six studies [ 27 – 29 , 31 , 32 , 35 ] with 2971 cases and 3150 controls. Random-effects models were used to calculate the pooled ORs.…”

Genetic association between germline JAK2polymorphisms and myeloproliferative neoplasms in Hong Kong Chinese population: a case–control study

“…Multiple comparisons were corrected by 50,000 permutations to give the P emp value. e These three SNPs (S8, S9 and S13) were directly genotyped in this study while the rest were imputed by Beagle v3.2 [ 41 ].…”

Association of High Myopia with Crystallin Beta A4 (CRYBA4) Gene Polymorphisms in the Linkage-Identified MYP6 Locus

“…This variation in the LD measures give rise to different boundaries between two LD blocks (Blocks 2 and 3; Figure 1) for these two Chinese populations. This fine-scale variation in LD patterns is not uncommon because LD is influenced by population histories among other things, as has also been observed in some of our previous studies [24]–[26].…”

The G allele of the IGF1 rs2162679 SNP is a potential protective factor for any myopia: Updated systematic review and meta-analysis

“…Among these SNPs, seven were tested in at least three studies and then were included in the meta-analysis. The study subjects were Chinese [ 29 , 31 , 32 , 34 , 35 ], Japanese [ 27 , 28 ], Egyptian [ 33 ] and Polish [ 30 ] with sample sizes that ranged from 127 to 1339. The total sample size was 9546 (4596 individuals with any myopia and 4950 controls).…”

“…Rs12423791 was tested in six studies [ 27 – 29 , 31 , 32 , 35 ] with 2971 cases and 3150 controls. Random-effects models were used to calculate the pooled ORs.…”

Genetic association between germline JAK2polymorphisms and myeloproliferative neoplasms in Hong Kong Chinese population: a case–control study

“…Multiple comparisons were corrected by 50,000 permutations to give the P emp value. e These three SNPs (S8, S9 and S13) were directly genotyped in this study while the rest were imputed by Beagle v3.2 [ 41 ].…”