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the effect of rare variants should be statistically detectable as these effects ought to be carried by one of the common background haplotypes (59). Furthermore, common variants can act as significant modifiers of the effects of rare variants (60). Thus, rare variants that are functionally relevant are often identified by common variant associations (61–64). Altogether, it seems unlikely that we have missed such rare variant effects in our comprehensive approach. The possi- bility that the negative association finding is due to popula- tion stratification in our samples is also rather improbable because the validity and efficacy of our large and well-char- acterized study population for genetic longevity research have already been shown with the identification and valida- tion of previous association findings (26,32–34). Overall, our results suggest that there is no noteworthy influence of sequence variation in the CYP2C genes on human longevity in Germans.

Funding

This study was supported by the Faculty of Medicine (intramural research support), Christian-Albrechts-University Kiel; and the DFG Excellence Cluster “Inflammation at Interfaces.”

Acknowledgments

We thank all study participants for their cooperation. For excellent tech- nical assistance, we wish to acknowledge the laboratory personnel of the Institute of Clinical Molecular Biology and the members of the Popgen Biobank.

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