Q test revealed significant heterogeneity for hip OA under all 5 contrasts, so the random-effects model was chosen for calculating ORs. As for knee OA and hand OA, the use of random- or fixed-effects model was determined according to the principle above mentioned. As regards the source of significant heterogeneity, we found that after stratified analysis by ethnicity and source of control, the degree of the significance was alleviated or even eliminated in some subgroups, suggesting the possible origins of heterogeneity might contain but not limit to ethnicity and source of control.
Sensitivity analysis was carried out to reflect the influence of each dataset on the summary ORs by deleting each single study included in the meta-analysis one by one. No material change was observed in corresponding pooled ORs, which suggested that our overall results were stable and robust.
The possible publication bias was assessed with Begg funnel plot and Egger test. Funnel plot seemed symmetrical (Fig. 4), which was also supported by P value of Egger test (P = .056). Therefore, no significant publication bias existed in the present study.
The inconsistent results may be explained by the following aspects: the studied population varied in terms of ethnicity, age, gender, and lifestyle; restricted number of cases and controls might affect the study results; different criteria were used for selecting study participants; and interfering factors were not adjusted in all studies.
Since the present study included altogether 19973 cases and 33537 controls, our results were statistically more powerful than results in any single study. Nevertheless, some limitations of the present study should be addressed. First of all, the majority of included studies provided original data toward Caucasian population, which might reduce the representativeness of our findings in other ethnicity or in general population. Next, language limitation in search strategy might miss some potent reports in other languages, thus leading to possible publication bias not detected by Begg funnel plot or Egger test. Then, significant interstudy heterogeneity existed in the meta-analysis which inevitably affected the precision of our results although we adopted the random-effects model to calculate OR. Besides, about a half of included studies are modulated quality by NOS assessment and the high quality studies are relative small. Last but not least, due to the lack of available information, synergies between genetic and environmental factors were not discussed. Overall, the present study indicates that BMP-14 rs143383 polymorphism may be correlated with decreased risk of OA. However, better-designed studies covering more ethnicity groups as well as gene–gene and gene–environment interactions should be carried out to verify our results.
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