Limits...
Joint Effect of CFH and ARMS2/HTRA1 Polymorphisms on Neovascular Age-Related Macular Degeneration in Chinese Population.

Fang K, Gao P, Tian J, Qin X, Yu W, Li J, Chen Q, Huang L, Chen D, Hu Y, Li X - J Ophthalmol (2015)

Bottom Line: The joint effect that involved CFH rs1061170 and HTRA1 rs3793917 was shown statistically significant (P < 0.001) with the highest cross-validation consistency (10/10) and the best testing balanced accuracy (64.50%).Conclusions.Evidence that the joint effect that involved CFH and ARMS2/HTRA1 may contribute to the risk of neovascular AMD in Chinese population was obtained.

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology & Biostatistics, School of Public Health, Peking University Health Science Center, Beijing 100191, China.

ABSTRACT
Purpose. The etiology of neovascular age-related macular degeneration (nAMD) cannot be completely explained by identified environmental risk factors or single-locus gene variants. This study was to explore the potential interactions among gene variants on nAMD in Chinese population. Methods. 43 SNPs located in different genes were genotyped in 932 Chinese individuals (464 nAMD patients and 468 controls). We explored the potential interactions among gene variants using generalized multifactor dimensionality reduction (GMDR) algorithm and the method to measure the departure from the additivity model. Results. The joint effect that involved CFH rs1061170 and HTRA1 rs3793917 was shown statistically significant (P < 0.001) with the highest cross-validation consistency (10/10) and the best testing balanced accuracy (64.50%). In addition, based on the method to measure the departure from the additivity model, the synergy index (S) was 2.63 (1.09-6.38) and the attributable proportion due to interaction (AP) was 55.7% (21.4%-89.9%), which suggested that a common pathway may exist for these genes for nAMD. Those who carried CC for rs3793917 and TC/CC for rs1061170 were at the highest risk of nAMD (OR: 9.76, 95% CI: 4.65-20.51). Conclusions. Evidence that the joint effect that involved CFH and ARMS2/HTRA1 may contribute to the risk of neovascular AMD in Chinese population was obtained.

No MeSH data available.


Related in: MedlinePlus

ORs with contributions from different exposure categories marked according to the departure-from-the-additivity model.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4389821&req=5

fig2: ORs with contributions from different exposure categories marked according to the departure-from-the-additivity model.

Mentions: Among all the models evaluated by GMDR for the interactions, the two-factor set including rs3793917and rs1061170 has shown the highest cross-validation consistency (10/10) and the best testing balanced accuracy of 64.50% (P < 0.001) (Table 3). We then assessed the joint effect of rs3793917 and rs1061170 using the method of departure-from-additivity model. The synergy index (S) was significantly greater than 1, that is, 2.63 (1.09–6.38). AP was 55.7% (21.4%–89.9%) and RERI of the two genes was 5.44 (−1.71 to 12.59) (Table 4). For the association of the combined categories using rs3793917 and rs1061170 with nAMD, compared with the reference group, that is, GC/GG for rs3793917 and TT for rs1061170, three groups were significantly associated with nAMD after adjusting for age and gender (P < 0.05). The highest risk group was CC for rs3793917 and TC/CC for rs1061170 with the OR of 9.76 (4.65–20.51) (Figure 2). Sensitivity analysis was carried out to allow ten factors to be selected in the informative set. The best model remained unchanged, that is, the two-factor set including rs3793917 and rs1061170, which was shown the highest cross-validation consistency (10/10) and the best testing balanced accuracy of 64.50% (Supplementary Table S4).


Joint Effect of CFH and ARMS2/HTRA1 Polymorphisms on Neovascular Age-Related Macular Degeneration in Chinese Population.

Fang K, Gao P, Tian J, Qin X, Yu W, Li J, Chen Q, Huang L, Chen D, Hu Y, Li X - J Ophthalmol (2015)

ORs with contributions from different exposure categories marked according to the departure-from-the-additivity model.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4389821&req=5

fig2: ORs with contributions from different exposure categories marked according to the departure-from-the-additivity model.
Mentions: Among all the models evaluated by GMDR for the interactions, the two-factor set including rs3793917and rs1061170 has shown the highest cross-validation consistency (10/10) and the best testing balanced accuracy of 64.50% (P < 0.001) (Table 3). We then assessed the joint effect of rs3793917 and rs1061170 using the method of departure-from-additivity model. The synergy index (S) was significantly greater than 1, that is, 2.63 (1.09–6.38). AP was 55.7% (21.4%–89.9%) and RERI of the two genes was 5.44 (−1.71 to 12.59) (Table 4). For the association of the combined categories using rs3793917 and rs1061170 with nAMD, compared with the reference group, that is, GC/GG for rs3793917 and TT for rs1061170, three groups were significantly associated with nAMD after adjusting for age and gender (P < 0.05). The highest risk group was CC for rs3793917 and TC/CC for rs1061170 with the OR of 9.76 (4.65–20.51) (Figure 2). Sensitivity analysis was carried out to allow ten factors to be selected in the informative set. The best model remained unchanged, that is, the two-factor set including rs3793917 and rs1061170, which was shown the highest cross-validation consistency (10/10) and the best testing balanced accuracy of 64.50% (Supplementary Table S4).

Bottom Line: The joint effect that involved CFH rs1061170 and HTRA1 rs3793917 was shown statistically significant (P < 0.001) with the highest cross-validation consistency (10/10) and the best testing balanced accuracy (64.50%).Conclusions.Evidence that the joint effect that involved CFH and ARMS2/HTRA1 may contribute to the risk of neovascular AMD in Chinese population was obtained.

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology & Biostatistics, School of Public Health, Peking University Health Science Center, Beijing 100191, China.

ABSTRACT
Purpose. The etiology of neovascular age-related macular degeneration (nAMD) cannot be completely explained by identified environmental risk factors or single-locus gene variants. This study was to explore the potential interactions among gene variants on nAMD in Chinese population. Methods. 43 SNPs located in different genes were genotyped in 932 Chinese individuals (464 nAMD patients and 468 controls). We explored the potential interactions among gene variants using generalized multifactor dimensionality reduction (GMDR) algorithm and the method to measure the departure from the additivity model. Results. The joint effect that involved CFH rs1061170 and HTRA1 rs3793917 was shown statistically significant (P < 0.001) with the highest cross-validation consistency (10/10) and the best testing balanced accuracy (64.50%). In addition, based on the method to measure the departure from the additivity model, the synergy index (S) was 2.63 (1.09-6.38) and the attributable proportion due to interaction (AP) was 55.7% (21.4%-89.9%), which suggested that a common pathway may exist for these genes for nAMD. Those who carried CC for rs3793917 and TC/CC for rs1061170 were at the highest risk of nAMD (OR: 9.76, 95% CI: 4.65-20.51). Conclusions. Evidence that the joint effect that involved CFH and ARMS2/HTRA1 may contribute to the risk of neovascular AMD in Chinese population was obtained.

No MeSH data available.


Related in: MedlinePlus