Results

The whole sample of 1,384 German LLI, a subset of 616 centenarians, and a control group of 945 younger individuals were subjected to a gender-matched case–control analysis of 56 SNPs located in the CYP2C genes (CYP2C8, CYP2C9, CYP2C18, and CYP2C19). All SNPs were found to be in HWE (p > .001). Only one nominally significant association signal (rs11188059; p = .04) was observed in the analysis CCA of the centenarian sample (Table 1) that did not pass correc- tion for multiple testing (Bonferroni-adjusted p = 1, as- CCA suming 56 tests; see “Participants and Methods” and “Statistical Analysis”). In the entire longevity sample (1,384 LLI and 945 controls), none of the tested SNPs showed a

With the applied approach, we are likely to have captured all common variation present in the analyzed samples for the CYP2C gene region. Acknowledging that the selected markers might be insufficient to tag the genetic variation comprehensively, we cannot rule out the presence of rare polymorphisms that could influence longevity. However, with the consideration of haplotype differences, if present,

Table 1. Association Statistics for 56 SNPs Located in the CYP2C Gene Region (for the centenarian subset)

Position on CHR 10 Gene SNP (GRCh37/hg19) Min AF Cases Min AF Controls p Bonferroni-Adjusted p CCA CCA CYP2C18 rs10736086 96441650 .489 .503 .45 1 rs12249418 96442917 .242 .215 .08 1 rs1575934 96445609 .464 .448 .36 1 rs7896133 96464730 .059 .069 .24 1 rs11188059 96468899 .106 .131 .04 1 rs7914753 96486504 .464 .448 .36 1 rs2281891 96493058 .164 .164 .99 1 rs1042192 96495284 .166 .167 .97 1 rs1042194 96495484 .164 .163 .92 1 rs1326830 96495793 .008 .012 .28 1 CYP2C19 rs12248560 96521657 .241 .216 .11 1 rs4986894 96522365 .164 .165 .95 1 rs6583954 96534263 .166 .166 .99 1 rs4388808 96536056 .158 .168 .47 1 rs7088784 96541373 .059 .068 .31 1 rs1322179 96575242 .164 .164 .99 1 rs10786172 96581094 .334 .344 .54 1 rs12253253 96582156 .241 .213 .07 1 rs7915414 96599510 .223 .232 .54 1 rs1555474 96605327 .464 .450 .44 1 rs4917623 96609568 .491 .502 .55 1 rs11592225 96627191 .143 .136 .59 1 CYP2C9 rs2475377 96690371 .044 .049 .53 1 rs4918758 96697252 .379 .381 .93 1 rs9332105 96698925 .186 .181 .71 1 rs9332113 96700402 .187 .181 .68 1 rs12772884 96700630 .386 .416 .10 1 rs1799853 96702047 .122 .125 .82 1 rs12572351 96703220 .186 .180 .65 1 rs4918766 96711884 .380 .377 .87 1 rs2475376 96712400 .148 .149 .92 1 rs2153628 96723424 .236 .212 .11 1 rs1856908 96732731 .339 .362 .20 1 rs9332197 96740908 .038 .049 .14 1 rs1057910 96741053 .058 .065 .44 1 rs1934967 96741426 .191 .211 .17 1 rs2153629 96741795 .135 .129 .66 1 rs9332222 96744064 .134 .125 .46 1 rs1057911 96748737 .058 .066 .42 1 rs9332242 96748893 .134 .125 .46 1 rs9332245 96749181 .063 .068 .52 1 rs4918797 96750251 .196 .196 .98 1 CYP2C8 rs1934954 96792202 .090 .079 .27 1 rs11572181 96795046 .061 .052 .29 1 rs1058932 96796861 .201 .197 .81 1 rs1934952 96797500 .344 .346 .92 1 rs10509681 96798749 .118 .107 .36 1 rs2275620 96802598 .345 .372 .12 1 rs1891073 96804911 .305 .327 .19 1 rs11572139 96808886 .302 .296 .70 1 rs6583967 96814475 .301 .294 .70 1 rs11572127 96814689 .043 .049 .45 1 rs1058930 96818119 .052 .059 .41 1 rs10882525 96825332 .353 .333 .24 1 rs17110453 96829529 .146 .150 .73 1

Notes: Centenarian subset: 616 German centenarians = 100–109 years; 945 younger controls = 60–75 years; CHR 10 = chromosome 10; GRCh37 = Genome Reference Consortium Human genome build 37; hg19 = release of the February 2009 human genome browser, UCSC version hg19; Min AF = minor allele frequency; p = p value obtained from an allele-based case-control comparison using a c2 test with 1 df; SNP = single nucleotide polymorphism. CCA Bold indicates SNP showed a nominally significant association signal in the analysis of the centenarian sample but did not pass correction for multiple testing.

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