Estimated mean differences in plasma IGF-I levels associated with IGF-I SNP variants relative to estimated mean IGF-I levels for reference genotypes (italicized) based on linear regression models for premenopausal Caucasian and African American women
| IGF-I SNP* | IGF-I location | Caucasians | African Americans | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| LD block† | Diplotype group (position)† | MAF (%)‡ | Genotype | n§ | Mean differences or means, ng/mL (95% CI)∥ | LD block† | Diplotype group (position)† | MAF (%)‡ | Genotype | n§ | Mean differences or means, ng/mL (95% CI)∥ | ||||||||||||
| rs35767 | Upstream | Outside | 1 (1) | 16.0 | AG, AA | 116 | 5 (−7 to 18) | 1 | 1 (1) | 40.8 | AA | 99 | −1 (−19 to 17) | ||||||||||
| AG | 264 | −2 (−16 to 11) | |||||||||||||||||||||
| GG | 280 | 171 (164-177) | GG | 205 | 166 (156-176) | ||||||||||||||||||
| rs5742612 | Upstream | — | — | 3.9 | AG, GG | 30 | 21 (−1 to 42) | — | — | 3.3 | AG, GG | 35 | 5 (−20 to 31) | ||||||||||
| AA | 368 | 171 (165-177) | AA | 536 | 164 (158-171) | ||||||||||||||||||
| rs5742614 | Intron 1 | — | — | 1.8 | CG | 14 | 18 (−14 to 49) | 1 | 1 (2) | 11.5 | CG, CC | 124 | 8 (−6 to 23) | ||||||||||
| GG | 385 | 172 (166-178) | GG | 444 | 163 (156-170) | ||||||||||||||||||
| rs3729846 | Exon 2 | — | — | 0 | — | — | 0.8 | CT | 9 | 33 (−16 to 82) | |||||||||||||
| CC | 399 | 172 (166-178) | CC | 557 | 164 (158-170) | ||||||||||||||||||
| rs12821878 | Intron 2 | 1 | 2 (1) | 22.7 | AA | 21 | 0 (−26 to 27) | Outside | 1 (3) | 5.8 | AG, AA | 64 | −15 (−34 to 5) | ||||||||||
| AG | 139 | 5 (−8 to 17) | |||||||||||||||||||||
| GG | 237 | 171 (163-178) | GG | 505 | 167 (160-173) | ||||||||||||||||||
| rs10860869 | Intron 2 | 1 | — | 29.1 | TT | 31 | −5 (−28 to 17) | Outside | 2 (1) | 32.3 | TT | 59 | 11 (−10 to 32) | ||||||||||
| AT | 170 | 6 (−6 to 18) | AT | 249 | 12 (−1 to 25) | ||||||||||||||||||
| AA | 196 | 170 (162-179) | AA | 262 | 158 (149-167) | ||||||||||||||||||
| rs1019731 | Intron 2 | 1 | 2 (2) | 12.3 | AC, AA | 93 | 10 (−4 to 23) | — | — | 3.4 | AC | 39 | −10 (−34 to 14) | ||||||||||
| CC | 304 | 170 (164-177) | CC | 528 | 165 (159-172) | ||||||||||||||||||
| rs7956547 | Intron 2 | 1 | 2 (3) | 27.3 | CC | 29 | −5 (−28 to 18) | 2 | 2 (2) | 26.2 | CC | 43 | 8 (−16 to 32) | ||||||||||
| CT | 160 | 2 (−10 to 14) | CT | 210 | 10 (−3 to 23) | ||||||||||||||||||
| TT | 209 | 172 (164-180) | TT | 314 | 160 (152-168) | ||||||||||||||||||
| rs5742626 | Intron 2 | — | — | 0.5 | CT | 4 | −3 (−61 to 54) | 2 | 2 (3) | 7.2 | CT, CC | 78 | −8 (−26 to 9) | ||||||||||
| TT | 394 | 172 (166-178) | TT | 491 | 166 (159-173) | ||||||||||||||||||
| rs17880975 | Intron 2 | — | — | 0.1 | AG | 1 | −78 (−193 to 37) | — | — | 2.3 | AG | 26 | 8 (−21 to 38) | ||||||||||
| GG | 395 | 173 (167-178) | GG | 540 | 165 (158-171) | ||||||||||||||||||
| rs2033178 | Intron 2 | 2 | 3 (1) | 6.2 | AG, AA | 47 | 5 (−13 to 22) | — | — | 4.7 | AG, AA | 50 | −24 (−46 to −3) | ||||||||||
| GG | 349 | 172 (166-178) | GG | 513 | 167 (161-174) | ||||||||||||||||||
| rs17884646 | Intron 2 | — | — | 0 | TT | 397 | 172 (166-178) | — | — | 0 | TT | 570 | 165 (159-171) | ||||||||||
| rs5742657 | Intron 2 | — | — | 2.2 | AG, GG | 17 | 18 (−11 to 46) | 2 | — | 12.1 | AG, GG | 128 | 3 (−11 to 18) | ||||||||||
| AA | 383 | 171 (166-177) | AA | 440 | 164 (157-170) | ||||||||||||||||||
| rs5742663 | Intron 2 | — | — | 0.1 | GT | 1 | 12 (−103 to 127) | 2 | — | 11.6 | GT, GG | 123 | 8 (−6 to 23) | ||||||||||
| TT | 396 | 172 (167-178) | TT | 444 | 163 (156-170) | ||||||||||||||||||
| rs11829586 | Intron 2 | — | — | 2.3 | AG | 18 | 16 (−12 to 43) | 2 | — | 11.5 | AG, AA | 121 | 7 (−8 to 22) | ||||||||||
| GG | 380 | 172 (166-178) | GG | 445 | 163 (156-170) | ||||||||||||||||||
| rs4764884 | Intron 2 | 2 | — | 25.7 | TT | 25 | −16 (−40 to 8) | 2 | 2 (4) | 23.7 | TT | 34 | 10 (−16 to 36) | ||||||||||
| CT | 153 | 0 (−12 to 12) | CT | 200 | 5 (−8 to 18) | ||||||||||||||||||
| CC | 218 | 173 (165-181) | CC | 333 | 162 (154-170) | ||||||||||||||||||
| rs5742683 | Intron 2 | — | — | 0.1 | AG | 1 | 12 (−102 to 127) | 2 | — | 10.6 | AG, GG | 113 | 5 (−11 to 20) | ||||||||||
| AA | 396 | 172 (166-178) | AA | 454 | 164 (157-171) | ||||||||||||||||||
| rs17884626 | Exon 3 | — | — | 0 | — | — | 1.0 | CT | 11 | 13 (−31 to 57) | |||||||||||||
| CC | 399 | 172 (167-178) | CC | 559 | 164 (158-171) | ||||||||||||||||||
| rs5009837 | Intron 3 | 2 | — | 30.3 | TT | 36 | −6 (−27 to 15) | Outside | 2 (5) | 41.3 | TT | 105 | 8 (−9 to 26) | ||||||||||
| CT | 167 | 6 (−6 to 18) | CT | 260 | 10 (−3 to 24) | ||||||||||||||||||
| CC | 192 | 170 (162-178) | CC | 203 | 158 (148-168) | ||||||||||||||||||
| rs17727841 | Intron 3 | 2 | 3 (2) | 19.1 | CC | 15 | −4 (−35 to 27) | — | — | 4.7 | CG, CC | 49 | 23 (1-44) | ||||||||||
| CG | 123 | −4 (−17 to 8) | |||||||||||||||||||||
| GG | 261 | 174 (167-181) | GG | 520 | 163 (156-169) | ||||||||||||||||||
| rs4764883 | Intron 3 | 2 | — | 30.9 | CC | 37 | −8 (−29 to 12) | 3 | — | 45.8 | TT | 132 | −12 (−29 to 5) | ||||||||||
| CT | 167 | 4 (−8 to 17) | CT | 248 | −11 (−25 to 3) | ||||||||||||||||||
| TT | 186 | 171 (163-179) | CC | 180 | 173 (162-183) | ||||||||||||||||||
| rs9308315 | Intron 3 | 2 | — | 28.2 | AA | 28 | −16 (−39 to 7) | 3 | 3 (1) | 49.8 | TT | 150 | −12 (−28 to 5) | ||||||||||
| AT | 166 | 3 (−9 to 15) | AT | 262 | −11 (−26 to 4) | ||||||||||||||||||
| TT | 201 | 172 (164-180) | AA | 152 | 173 (161-185) | ||||||||||||||||||
| rs978458 | Intron 3 | 2 | 3 (3) | 28.0 | TT | 28 | −13 (−37 to 10) | 3 | — | 37.5 | TT | 83 | 9 (−10 to 28) | ||||||||||
| CT | 164 | 4 (−8 to 16) | CT | 259 | 7 (−6 to 20) | ||||||||||||||||||
| CC | 202 | 172 (163-180) | CC | 224 | 160 (151-170) | ||||||||||||||||||
| rs5742692 | Intron 3 | — | — | 2.1 | 3 | 3 (2) | 11.7 | GG | 11 | 14 (−31 to 58) | |||||||||||||
| AG | 17 | 18 (−11 to 46) | AG | 111 | 4 (−12 to 19) | ||||||||||||||||||
| AA | 382 | 171 (166-177) | AA | 444 | 164 (157-170) | ||||||||||||||||||
| rs11111262 | Intron 3 | 2 | — | 9.9 | AG, AA | 76 | −4 (−19 to 10) | — | — | 2.7 | AG, AA | 27 | 40 (11-68) | ||||||||||
| GG | 321 | 173 (167-180) | GG | 536 | 163 (157-169) | ||||||||||||||||||
| rs1520220 | Intron 3 | 2 | 3 (4) | 19.1 | GG | 13 | −33 (−65 to 0) | 3 | 3 (3) | 34.7 | GG | 73 | 10 (−9 to 29) | ||||||||||
| CG | 124 | 7 (−6 to 19) | CG | 250 | 6 (−7 to 19) | ||||||||||||||||||
| CC | 258 | 171 (164-178) | CC | 245 | 161 (151-170) | ||||||||||||||||||
| rs3730204 | Exon 4; 3′ untranslated | — | — | 2.3 | CT | 18 | −24 (−52 to 3) | — | — | 0.3 | CT | 3 | 6 (−79 to 90) | ||||||||||
| TT | 378 | 173 (168-179) | TT | 562 | 165 (159-171) | ||||||||||||||||||
| rs6214 | Exon 4; 3′ untranslated | Outside | 3 (5) | 39.8 | TT | 67 | 17 (0-34) | Outside | 3 (4) | 45.2 | CC | 124 | −3 (−20 to 14) | ||||||||||
| CT | 183 | −2 (−14 to 11) | CT | 263 | −4 (−18 to 10) | ||||||||||||||||||
| CC | 148 | 170 (161-180) | TT | 178 | 167 (156-178) | ||||||||||||||||||
| rs6219 | Exon 4; 3′ untranslated | 3 | 4 (1) | 10.0 | CT, TT | 78 | −6 (−20 to 9) | 4 | 4 (1) | 9.1 | CT, TT | 94 | 16 (−1 to 32) | ||||||||||
| CC | 321 | 174 (167-180) | CC | 475 | 162 (155-169) | ||||||||||||||||||
| rs2946834 | Downstream | 3 | 4 (2) | 33.0 | AA | 39 | −7 (−28 to 13) | 4 | 4 (2) | 49.3 | AA | 142 | 16 (0-33) | ||||||||||
| AG | 181 | 1 (−11 to 13) | AG | 279 | 2 (−12 to 17) | ||||||||||||||||||
| GG | 175 | 172 (164-181) | GG | 147 | 159 (147-171) | ||||||||||||||||||
↵* Represent tag SNPs except for 2 SNPs that were selected a priori: rs3729846 (Thr52Thr) and rs17884626 (Ala115Thr).
↵† LD blocks consist of SNPs with MAF ≥ 5% in strong LD (95% of pairwise SNP comparisons with one-sided 95% CIs for D′ within 0.70-0.98). Group refers to SNP combination for diplotype estimation; position refers to SNP order in each group. SNPs were excluded from diplotype estimation based on either Tagger algorithm (r2 ≥ 0.8) or MAF < 5% for tag SNPs or MAF < 3% for SNPs selected a priori. For African Americans, rs9308315 was the substitute for rs4764883 (Hardy-Weinberg P < 0.01).
↵‡ Based on total n = 402 (Caucasians) and total n = 582 (African Americans).
↵§ Caucasians: n = 401, excluded 1 missing plasma IGF-I. African Americans: n = 574, excluded 8 missing plasma IGF-I.
↵∥ Mean plasma IGF-I levels for reference genotypes estimated from linear regression intercepts are italicized in the last row for each SNP. Mean differences in plasma IGF-I levels for heterozygous and homozygous variants relative to reference genotypes were estimated from β values in linear regression models.