Several limitations are important to take into account when interpreting our results. There are likely other factors associated with survival free of neurological disease for which we did not collect information; as such, we cannot rule out the possibility that the associations between SNCA and survival free of neurological disease that we identified may be due in part to confounding factors. Also, owing to the exploratory nature of the study, we made no adjustment for multiple testing. The statistically significant decreasing frequencies of the minor allele for rs10014396 and rs3775439 as age increased in controls would not have remained significant after such an adjustment (P<0.0058 considered significant after permutation adjustment for multiple testing), highlighting the need for validation in independent series of healthy individuals. Our sample size of more than 700 controls free of neurological disease is relatively small, and therefore the possibility of Type II error (i.e. a false negative association), particularly after adjustment for multiple testing, is important to consider.

Acknowledgments

We would like to thank all those who have contributed to our research.

Author Contributions

MMC, RJU, ZKW, NRGR and OAR conceived and designed the experiments. AISO and OAR performed the experiments. MGH and NND analyzed the data. OAR, ZKW and NRGR contributed reagents/materials/analysis tools. MGH and OAR wrote the paper.

References

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