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. 2024 Sep 2;2:63. doi: 10.1038/s44276-024-00077-3

Table 3.

Top 5 SNPS for which interaction between calcium intake and that specific genetic variant in relation to CRC outcomes was observed.

MULTIPLICATIVE INTERACTIONS
Interaction GxE (calcium and CaSR)
All-cause mortality CRC-specific mortality
Dietary calcium sex- and cohort- specific quartiles Dietary calcium sex- and cohort- specific quartiles
SNP N/events RERIa 95%CI P-valueb MAF SNP N/events RERIa 95%CI P-valueb MAF
3:121910706_A/G rs1553309 11173/3841 1.04 1.00–1.08 0.075 0.42 3:121903842_C/A rs6780443d 11173/2499 1.08 1.02–1.14 0.012 0.24
3:121914667_T/C rs6764205c 11173/3841 1.04 1.00–1.09 0.049 0.30 3:121909830_C/G rs17282008d 11173/2499 1.07 1.01–1.14 0.018 0.24
3:121921700_T/C rs46780431219c 11173/3841 1.05 1.00–1.09 0.048 0.30 3:121932422_C/T rs62269066e 11173/2499 1.06 1.00–1.11 0.038 0.36
3:121922863_A/G rs4678045c 11173/3841 1.05 1.00–1.09 0.048 0.30 3:121936453_G/A rs11713280 11173/2499 1.12 1.01–1.23 0.026 0.07
3:121936453_G/A rs11713280 11173/3841 1.09 1.01–1.18 0.023 0.07 3:121966952_C/T rs7637874d 11173/2499 1.07 1.01–1.13 0.031 0.24
Supplement ≥ 1 versus < 1 pill Supplement ≥ 1 versus < 1 pill
3:121913708_C/T rs17282015e 9207/3210 1.24 1.09–1.42 0.0009 0.36 3:121913708_C/T rs17282015e 9207/1999 1.25 1.07–1.47 0.006 0.36
3:121917298_T/C rs11708053e 9207/3210 1.25 1.10–1.42 0.0007 0.36 3:121917298_T/C rs11708053e 9207/1999 1.26 1.07–1.47 0.005 0.36
3:121917387_A/G rs11711698e 9207/3210 1.25 1.10–1.42 0.0007 0.36 3:121917387_A/G rs11711698e 9207/1999 1.25 1.07–1.47 0.005 0.36
3:121932422_C/T rs62269066e 9207/3210 1.25 1.10–1.43 0.0006 0.36 3:121932422_C/T rs62269066e 9207/1999 1.24 1.06–1.46 0.008 0.36
3:121936453_G/A rs11713280 9207/3210 1.49 1.19–1.87 0.0006 0.07 3:121936453_G/A rs11713280 9207/1999 1.6 1.21–2.11 0.0009 0.07
Total calcium intake sex- and cohort- specific quartiles Total calcium intake sex- and cohort- specific quartiles
3:121992825_C/T rs3804594f 4646/1695 0.87 0.78–0.97 0.011 0.08 3:121994941_G/A rs2279802f 4646/1005 0.81 0.70–0.94 0.005 0.08
3:121995415_C/T rs13093602f 4646/1695 0.87 0.78–0.97 0.013 0.08 3:121995415_C/T rs13093602f 4646/1005 0.81 0.70–0.94 0.005 0.08
3:121996810_T/A rs1827381f 4646/1695 0.87 0.78–0.97 0.013 0.08 3:121996810_T/A rs1827381f 4646/1005 0.81 0.70–0.94 0.005 0.08
3:121997268_T/C rs3792291f 4646/1695 0.87 0.78–0.97 0.013 0.08 3:121997268_T/C rs3792291f 4646/1005 0.81 0.70–0.94 0.005 0.08
3:121999059_G/A rs2055427f 4646/1695 0.87 0.78–0.97 0.012 0.08 3:121999059_G/A rs2055427f 4646/1005 0.81 0.70–0.94 0.005 0.08
ADDITIVE INTERACTIONS
Dietary calcium sex- and cohort- specific quartiles Dietary calcium sex- and cohort- specific quartiles
3:121921700_T/C rs4678043c 11173/3841 0.04 −0.00–0.08 0.068 0.30 3:121903842_C/A rs6780443d 11173/2499 0.06 0.02–0.11 0.013 0.24
3:121922863_A/G rs4678045c 11173/3841 0.04 −0.00–0.09 0.070 0.30 3:121909830_C/G rs17282008d 11173/2499 0.06 0.01–0.11 0.018 0.24
3:121936453_G/A rs11713280 11173/3841 0.07 0.02–0.13 0.015 0.07 3:121936453_G/A rs11713280 11173/2499 0.09 0.03–0.15 0.012 0.07
3:121996235_G/A rs77663377 11173/3841 0.07 −0.01–0.14 0.080 0.15 3:121966952_C/T rs7637874d 11173/2499 0.06 0.01–0.10 0.037 0.24
3:122005273_A/G rs34042920 11173/3841 0.04 −0.01–0.10 0.107 0.10 3:121996235_G/A rs77663377 11173/2499 0.09 0.003–0.17 0.051 0.15
Supplement ≥ 1 versus < 1 pill Supplement ≥ 1 versus < 1 pill
3:121903842_C/A rs6780443d 9207/3210 0.22 0.09–0.36 0.0009 0.24 3:121903842_C/A rs6780443d 9207/1999 0.23 0.05–0.41 0.010 0.24
3:121909830_C/G rs17282008d 9207/3210 0.22 0.09–0.36 0.0009 0.24 3:121909830_C/G rs17282008d 9207/1999 0.23 0.05–0.41 0.009 0.24
3:121932422_C/T rs62269066e 9207/3210 0.21 0.10–0.32 0.00006 0.36 3:121917298_T/C rs11708053e 9207/1999 0.22 0.07–0.36 0.003 0.36
3:121936453_G/A rs11713280 9207/3210 0.40 0.15–0.64 0.0009 0.07 3:121936453_G/A rs11713280 9207/1999 0.51 0.18–0.84 0.002 0.07
3:121966952_C/T rs7637874d 9207/3210 0.22 0.08–0.36 0.0009 0.24 3:121966952_C/T rs76377874d 9207/1999 0.22 0.04–0.09 0.015 0.24
Total calcium intake sex- and cohort- specific quartiles Total calcium intake sex- and cohort- specific quartiles
3:121984792_G/A rs17197671g 4646/1695 0.07 0.004–0.13 0.015 0.14 3:121930454_C/G rs75473459h 4646/1005 0.10 0.02–0.18 0.021 0.11
3:121988851_G/C rs6783855g 4646/1695 0.07 0.004–0.13 0.015 0.14 3:121917298_T/C rs11708053e 4646/1005 0.08 0.01–0.15 0.030 0.36
3:121990800_T/C rs1604446g 4646/1695 0.07 0.004–0.13 0.015 0.14 3:121917387_A/G rs11711698e 4646/1005 0.08 0.01–0.15 0.032 0.36
3:122002178_T/C rs2134224g 4646/1695 0.07 0.003–0.13 0.014 0.14 3:121939743_C/T rs36004543h 4646/1005 0.11 0.03–0.19 0.004 0.12
3:122005273_A/G rs34042920g 4646/1695 0.09 0.03–0.16 0.005 0.10 3:121958475_G/A rs62269089h 4646/1005 0.10 0.01–0.18 0.020 0.11

aModels were adjusted for age at diagnosis, sex, cohort, and the first three principal components of genetic ancestry as well as main effects of calcium intake (dietary, supplemental or total) and SNPs. Sex- and cohort- specific quartiles as well as SNPs were entered as continuous variables for both the multiplicative as the additive interaction models.

bThe estimated effective number of independent tests among 325 SNPS was 35 based on the simple M approach. Therefore, p < 0.001 were considered statistically significant (n = 35; 0.05/35 = 0.001).

c,d,e,f,g,hCorrelated SNPS (r2 > 0.6).