Online Supplemental Figure 1: Linkage disequilibrium (LD) plot across the ADIPOQ locus plus 20kb upstream and 10kb downstream. The horizontal black line depicts the 47kb DNA segment of chromosome 3q27 analyzed in our sample, with the ADIPOQ gene displayed by the blue horizontal line above it (known gene id: D45371). The locations of the 35 SNPs included in this analysis are indicated below the black line, with the 22 tag SNPs in black hash marks above their rs number designations. An LD plot is in the bottom part of the figure based on the measure D’: each square represents the magnitude of LD for a single pair of markers, with red color indicating LD that is strong and statistically significant. Figure prepared using the program LocusView 2.0 (T. Petryshen, A. Kirby, M. Ainscow).
Online Supplemental Table 1:
n / Mean (SD) or %
Sex (% female) / 2528 / 53
Age (years) / 2414 / 54 (9.8)
Body mass index (kg/m²) / 2403 / 27.4 (5.0)
Waist circumference (inches) / 2411 / 36.5 (5.7)
Fasting glucose (mg/dl) / 2382 / 100.1 (26.3)
Fasting insulin (µU/ml) / 2275 / 30.0 (12.3)
HOMA-IR / 2275 / 7.7 (4.9)
Gutt 0-120 ISI / 2163 / 25.7 (7.5)
Hemoglobin A1C (%) / 1758 / 5.4 (1.0)
SD: standard deviation
HOMA-IR: homeostasis model insulin resistance calculated by [fasting glucose x fasting insulin]/22.5
Gutt 0-120 ISI: insulin sensitivity index calculated with the 2h oral glucose tolerance test
Online Supplemental Table 2:
n / Mean (SD) or %
Sex (% female) / 1023 / 50
Age (years) / 1012 / 59 (9.1)
Body mass index (kg/m²) / 1005 / 28.3 (5.1)
Waist circumference (inches) / 1001 / 39.1 (5.3)
Subcutaneous Adipose Tissue (cm³) / 1023 / 2984.8 (1310.1)
Visceral Adipose Tissue (cm³) / 1023 / 2138.8 (1100.5)
Online Supplemental Table 3
SNP / Position
(NCBI 35) / MAF
(CEU HapMap) / Alleles
(Major: minor) / tag SNP / r²
rs6810075 / 188031267 / 0.37 / T:C / rs182052 / 0.93
rs10937273 / 188032397 / 0.41 / G:A / rs10937273 / 1.00
rs12637534 / 188032903 / 0.06 / A:G / rs16861194 / 0.87
rs1648707 / 188034413 / 0.37 / A:C / rs182052 / 1
rs6444168 / 188035559 / 0.12 / G:A / rs864265 / 0.93
rs864265 / 188036994 / 0.13 / G:T / rs864265 / 1
rs822387 / 188038739 / 0.10 / T:C / rs822387 / 1
rs16861194 / 188042127 / 0.07 / A:G / rs16861194 / 1
rs17300539 / 188042162 / 0.08 / G:A / rs17300539 / 1
rs266729 / 188042176 / 0.30 / C:G / rs266729 / 1
rs182052 / 188043484 / 0.35 / G:A / rs182052 / 1
rs822391 / 188046505 / 0.17 / T:C / rs822391 / 1
rs16861210 / 188049200 / 0.10 / G:A / rs822387 / 1
rs822394 / 188049430 / 0.08 / C:A / rs822396 / 0.89
rs822396 / 188049579 / 0.15 / A:G / rs822396 / 1
rs12495941 / 188050882 / 0.31 / G:T / rs12495941 / 1
rs7649121 / 188051487 / 0.23 / A:T / rs7649121 / 1
rs17366568 / 188053155 / 0.09 / G:A / rs17366568 / 1
rs1501299 / 188053825 / 0.27 / C:A / rs1501299 / 1
rs2241767 / 188053898 / 0.13 / A:G / rs3774262 / 1
rs3821799 / 188054188 / 0.46 / C:T / rs3821799 / 1
rs3774261 / 188054261 / 0.40 / G:A / rs6773957 / 1
rs3774262 / 188054516 / 0.13 / G:A / rs3774262 / 1
rs17366743 / 188054791 / 0.08 / T:C / rs17366743 / 1
rs6773957 / 188056407 / 0.40 / G:A / rs6773957 / 1
rs1063537 / 188056777 / 0.13 / C:T / rs3774262 / 1
rs2082940 / 188056866 / 0.13 / C:T / rs3774262 / 1
rs1063538 / 188056885 / 0.40 / C:T / rs6773957 / 1
rs1063539 / 188058094 / 0.13 / G:C / rs3774262 / 0.85
rs7639352 / 188061176 / 0.29 / C:T / rs6444175 / 1
rs6444175 / 188062446 / 0.29 / G:A / rs6444175 / 1
rs7628649 / 188068083 / 0.10 / C:T / rs7628649 / 1
rs17373414 / 188068229 / 0.11 / C:T / rs17373414 / 1
SNP: single nucleotide polymorphism identified by their rs number
MAF (CEU HapMap): minor allele frequency in the Caucasians of European descent in the HapMap
r²: r-square measure of linkage disequilibrium
Online Supplemental Table 4
Results of longitudinal and the exam 7 metabolic traits associations in the Framingham Offspring Study included in the ADIPOQ analysis (presented by trait and by SNP position order)SNP / Position (NCBI 35) / N / Alleles M/m / Mean ± SD M/M / Mean ± SD M/m / Mean ± SD m/m / P-value (adjusted for sex, age, age²) / empiric P-value* / P-value (adjusted for sex, age, age², BMI) / empiric P-value†
28-year Time-Averaged Mean Plasma Glucose (exam 1-7)
rs10937273 / 188032397 / 2353 / G/A / 99.16 ± 16.87 / 99.24 ± 17.23 / 100.19 ± 17.41 / 0.662 / 1.000 / 0.707 / 1.000
rs864265 / 188036994 / 2378 / G/T / 99.68 ± 17.75 / 98.94 ± 15.6 / 95.33 ± 10.6 / 0.118 / 0.823 / 0.271 / 0.985
rs822387 / 188038739 / 2455 / T/C / 99.47 ± 17.36 / 98.28 ± 14.12 / 99.7 ± 19.23 / 0.438 / 1.000 / 0.346 / 0.999
rs16861194 / 188042127 / 2447 / A/G / 99.42 ± 17.24 / 98.75 ± 15.67 / 99.07 ± 12.44 / 0.931 / 1.000 / 0.968 / 1.000
rs17300539 / 188042162 / 2426 / G/A / 99.57 ± 17.62 / 97.98 ± 13.24 / 99.88 ± 19.74 / 0.145 / 0.880 / 0.150 / 0.889
rs266729 / 188042176 / 2422 / C/G / 98.92 ± 15.70 / 100.1 ± 18.84 / 98.63 ± 17.05 / 0.366 / 0.999 / 0.339 / 0.998
rs182052 / 188043484 / 2455 / G/A / 98.85 ± 15.85 / 100.1 ± 18.24 / 98.34 ± 16.93 / 0.409 / 1.000 / 0.395 / 1.000
rs822391 / 188046505 / 2385 / T/C / 99.87 ± 18.18 / 98.79 ± 15.46 / 96.77 ± 10.88 / 0.081 / 0.687 / 0.136 / 0.858
rs822396 / 188049579 / 2456 / A/G / 99.71 ± 17.87 / 98.67 ± 15.36 / 96.92 ± 11.07 / 0.117 / 0.820 / 0.158 / 0.903
rs12495941 / 188050882 / 2356 / G/T / 99.25 ± 16.55 / 99.6 ± 17.87 / 99.47 ± 16.49 / 0.731 / 1.000 / 0.793 / 1.000
rs7649121 / 188051487 / 2454 / A/T / 98.79 ± 15.47 / 100.56 ± 19.87 / 99.52 ± 18.75 / 0.038 / 0.414 / 0.052 / 0.518
rs17366568 / 188053155 / 2412 / G/A / 99.59 ± 17.39 / 98.71 ± 16.02 / 95.33 ± 14.28 / 0.156 / 0.902 / 0.185 / 0.937
rs2241766 / 188053594 / 1842 / T/G / 99.16 ± 16.91 / 99.85 ± 16.45 / 99.69 ± 18.07 / 0.869 / 1.000 / 0.793 / 1.000
rs1501299 / 188053825 / 1792 / G/T / 99.93 ± 17.64 / 98.25 ± 14.9 / 101.4 ± 20.89 / 0.771 / 1.000 / 0.595 / 1.000
rs3821799 / 188054188 / 2453 / C/T / 99.65 ± 17.63 / 99.47 ± 17.27 / 98.25 ± 14.94 / 0.182 / 0.935 / 0.238 / 0.977
rs3774262 / 188054516 / 2454 / G/A / 99.37 ± 17.21 / 99.04 ± 16.21 / 97.78 ± 11.6 / 0.678 / 1.000 / 0.782 / 1.000
rs17366743 / 188054791 / 2460 / T/C / 98.96 ± 16.14 / 105.58 ± 27.56 / 101.29 ± NA / 0.0004 / 0.0045 / 0.0010 / 0.0145
rs6773957 / 188056407 / 2437 / G/A / 99.51 ± 17.34 / 99.31 ± 17.11 / 98.77 ± 15.78 / 0.752 / 1.000 / 0.736 / 1.000
rs6444175 / 188062446 / 2423 / G/A / 99.62 ± 17.5 / 98.71 ± 15.99 / 100.05 ± 18.25 / 0.901 / 1.000 / 0.735 / 1.000
rs13085499 / 188063542 / 2423 / A/G / 99.46 ± 17.42 / 99.68 ± 17.56 / 98.27 ± 15.07 / 0.276 / 0.986 / 0.350 / 0.999
rs7628649 / 188068083 / 2445 / C/T / 99.33 ± 17 / 99.23 ± 16.86 / 100.24 ± 18.21 / 0.955 / 1.000 / 0.966 / 1.000
rs17373414 / 188068229 / 2417 / C/T / 99.37 ± 17.33 / 99.12 ± 15.44 / 99.21 ± 21.71 / 0.511 / 1.000 / 0.531 / 1.000
Fasting Plasma Glucose (mg/dl)
rs10937273 / 188032397 / 2194 / G/A / 103.98 ± 28.42 / 103.98 ± 25.71 / 105.87 ± 26.11 / 0.311 / 0.991 / 0.581 / 1.000
rs864265 / 188036994 / 2216 / G/T / 104.75 ± 27.16 / 103.73 ± 25.22 / 99.89 ± 23.74 / 0.187 / 0.939 / 0.297 / 0.989
rs822387 / 188038739 / 2289 / T/C / 104.61 ± 27.26 / 102.12 ± 20.54 / 106.33 ± 32.25 / 0.307 / 0.990 / 0.307 / 0.990
rs16861194 / 188042127 / 2281 / A/G / 104.1 ± 26.17 / 104.76 ± 25.41 / 118.54 ± 67.87 / 0.133 / 0.851 / 0.146 / 0.880
rs17300539 / 188042162 / 2261 / G/A / 104.62 ± 27.42 / 102.08 ± 20.22 / 107.71 ± 32.91 / 0.269 / 0.985 / 0.351 / 0.999
rs266729 / 188042176 / 2256 / C/G / 104.2 ± 25.22 / 104.66 ± 27.5 / 103.38 ± 32.28 / 0.704 / 1.000 / 0.804 / 1.000
rs182052 / 188043484 / 2289 / G/A / 103.68 ± 24.01 / 105.03 ± 27.46 / 103.85 ± 32.2 / 0.667 / 1.000 / 0.298 / 0.989
rs822391 / 188046505 / 2223 / T/C / 104.96 ± 27.15 / 103.45 ± 25.45 / 103.27 ± 29.33 / 0.171 / 0.922 / 0.274 / 0.985
rs822396 / 188049579 / 2289 / A/G / 104.53 ± 25.86 / 103.59 ± 27.07 / 103.6 ± 30.22 / 0.299 / 0.989 / 0.394 / 1.000
rs12495941 / 188050882 / 2198 / G/T / 103.88 ± 27 / 104.82 ± 27.22 / 104.34 ± 22.99 / 0.383 / 1.000 / 0.634 / 1.000
rs7649121 / 188051487 / 2288 / A/T / 104.04 ± 26.01 / 105.16 ± 27.4 / 101.64 ± 26.75 / 0.922 / 1.000 / 0.647 / 1.000
rs17366568 / 188053155 / 2248 / G/A / 104.65 ± 26.68 / 103.69 ± 27.04 / 96 ± 13.39 / 0.122 / 0.830 / 0.168 / 0.920
rs2241766 / 188053594 / 1759 / T/G / 103.96 ± 26.43 / 105.39 ± 28.6 / 104.14 ± 20.69 / 0.519 / 1.000 / 0.414 / 1.000
rs1501299 / 188053825 / 1712 / G/T / 104.5 ± 26.96 / 103.52 ± 25.66 / 107.53 ± 30.05 / 0.542 / 1.000 / 0.788 / 1.000
rs3821799 / 188054188 / 2288 / C/T / 103.61 ± 26.39 / 104.79 ± 27.2 / 103.55 ± 24.1 / 0.654 / 1.000 / 0.593 / 1.000
rs3774262 / 188054516 / 2287 / G/A / 104.22 ± 26.46 / 104.36 ± 26.91 / 102.83 ± 16.82 / 0.740 / 1.000 / 0.584 / 1.000
rs17366743 / 188054791 / 2293 / T/C / 103.86 ± 25.79 / 110.55 ± 35.67 / 102 ± NA / 0.044 / 0.467 / 0.076 / 0.664
rs6773957 / 188056407 / 2275 / G/A / 103.53 ± 25.52 / 104.92 ± 27.82 / 103.96 ± 24.26 / 0.295 / 0.988 / 0.300 / 0.989
rs6444175 / 188062446 / 2258 / G/A / 104.13 ± 26.45 / 103.88 ± 26.25 / 106.53 ± 27.52 / 0.354 / 0.999 / 0.459 / 1.000
rs13085499 / 188063542 / 2259 / A/G / 103.63 ± 26.89 / 104.99 ± 27.24 / 103.46 ± 24.04 / 0.691 / 1.000 / 0.574 / 1.000
rs7628649 / 188068083 / 2280 / C/T / 104.29 ± 26.55 / 104.08 ± 26.05 / 102.24 ± 16.67 / 0.945 / 1.000 / 0.922 / 1.000
rs17373414 / 188068229 / 2253 / C/T / 104.47 ± 27.08 / 103.53 ± 23.68 / 103.5 ± 33.62 / 0.238 / 0.976 / 0.369 / 0.999
Fasting Plasma Insulin (µU/ml)
rs10937273 / 188032397 / 2119 / G/A / 14.56 ± 9.56 / 14.72 ± 7.82 / 15.51 ± 9.27 / 0.049 / 0.499 / 0.188 / 0.941
rs864265 / 188036994 / 2140 / G/T / 14.81 ± 8.69 / 14.83 ± 8.77 / 13.89 ± 7.98 / 0.434 / 1.000 / 0.697 / 1.000
rs822387 / 188038739 / 2211 / T/C / 14.8 ± 8.3 / 14.78 ± 10.34 / 14.32 ± 7.35 / 0.564 / 1.000 / 0.609 / 1.000
rs16861194 / 188042127 / 2203 / A/G / 14.74 ± 8.63 / 14.96 ± 8.7 / 18.5 ± 10.2 / 0.187 / 0.939 / 0.316 / 0.993
rs17300539 / 188042162 / 2183 / G/A / 14.83 ± 8.34 / 14.59 ± 10.42 / 14.49 ± 6.91 / 0.287 / 0.988 / 0.433 / 1.000
rs266729 / 188042176 / 2179 / C/G / 15.07 ± 8.61 / 14.42 ± 8.84 / 14.26 ± 7.68 / 0.049 / 0.500 / 0.255 / 0.982
rs182052 / 188043484 / 2210 / G/A / 15.07 ± 8.57 / 14.55 ± 8.93 / 14.53 ± 7.9 / 0.228 / 0.971 / 0.610 / 1.000
rs822391 / 188046505 / 2147 / T/C / 14.78 ± 8.81 / 15.04 ± 8.66 / 14.15 ± 7.3 / 0.838 / 1.000 / 0.636 / 1.000
rs822396 / 188049579 / 2211 / A/G / 14.82 ± 8.77 / 14.8 ± 8.56 / 14.01 ± 7.16 / 0.361 / 0.999 / 0.574 / 1.000
rs12495941 / 188050882 / 2120 / G/T / 14.69 ± 9.52 / 14.89 ± 8.28 / 14.99 ± 7.72 / 0.076 / 0.664 / 0.231 / 0.973
rs7649121 / 188051487 / 2209 / A/T / 14.94 ± 8.46 / 14.55 ± 9.19 / 13.98 ± 7.04 / 0.155 / 0.900 / 0.356 / 0.999
rs17366568 / 188053155 / 2172 / G/A / 14.84 ± 8.75 / 14.83 ± 8.47 / 12.84 ± 7.39 / 0.548 / 1.000 / 0.503 / 1.000
rs2241766 / 188053594 / 1694 / T/G / 14.77 ± 9.07 / 14.62 ± 7.89 / 13.14 ± 5.75 / 0.594 / 1.000 / 0.883 / 1.000
rs1501299 / 188053825 / 1649 / G/T / 14.58 ± 8.04 / 14.94 ± 10.06 / 14.75 ± 7.65 / 0.492 / 1.000 / 0.829 / 1.000
rs3821799 / 188054188 / 2209 / C/T / 14.44 ± 7.69 / 15.03 ± 9.39 / 14.71 ± 8.12 / 0.452 / 1.000 / 0.431 / 1.000
rs3774262 / 188054516 / 2208 / G/A / 14.88 ± 8.89 / 14.51 ± 7.89 / 14.19 ± 7 / 0.552 / 1.000 / 0.861 / 1.000
rs17366743 / 188054791 / 2214 / T/C / 14.76 ± 8.23 / 15.37 ± 14.31 / 5.74 ± NA / 0.769 / 1.000 / 0.527 / 1.000
rs6773957 / 188056407 / 2196 / G/A / 14.61 ± 7.83 / 15 ± 9.67 / 14.7 ± 7.3 / 0.502 / 1.000 / 0.622 / 1.000
rs6444175 / 188062446 / 2180 / G/A / 14.57 ± 7.85 / 15.01 ± 9.86 / 15.22 ± 7.73 / 0.240 / 0.977 / 0.599 / 1.000
rs13085499 / 188063542 / 2181 / A/G / 14.58 ± 7.9 / 15.01 ± 9.31 / 14.58 ± 8.15 / 0.957 / 1.000 / 0.867 / 1.000
rs7628649 / 188068083 / 2201 / C/T / 14.89 ± 8.91 / 14.49 ± 7.83 / 13.26 ± 5.79 / 0.413 / 1.000 / 0.575 / 1.000
rs17373414 / 188068229 / 2176 / C/T / 14.84 ± 8.99 / 14.6 ± 7.49 / 15.06 ± 7.63 / 0.752 / 1.000 / 0.917 / 1.000
HOMA-IR
rs10937273 / 188032397 / 2119 / G/A / 3.96 ± 3.67 / 3.89 ± 2.61 / 4.27 ± 3.84 / 0.051 / 0.511 / 0.196 / 0.947
rs864265 / 188036994 / 2140 / G/T / 4 ± 3.37 / 3.97 ± 2.9 / 3.61 ± 2.7 / 0.398 / 1.000 / 0.651 / 1.000
rs822387 / 188038739 / 2211 / T/C / 3.99 ± 3.09 / 3.94 ± 3.81 / 4 ± 3.22 / 0.483 / 1.000 / 0.497 / 1.000
rs16861194 / 188042127 / 2203 / A/G / 3.97 ± 3.24 / 3.93 ± 2.63 / 6.31 ± 7.54 / 0.163 / 0.913 / 0.283 / 0.987
rs17300539 / 188042162 / 2183 / G/A / 4 ± 3.1 / 3.88 ± 3.86 / 4.09 ± 3.21 / 0.231 / 0.973 / 0.344 / 0.999
rs266729 / 188042176 / 2179 / C/G / 4.05 ± 3.22 / 3.9 ± 3.27 / 3.83 ± 3.1 / 0.062 / 0.592 / 0.329 / 0.996
rs182052 / 188043484 / 2210 / G/A / 4.05 ± 3.22 / 3.91 ± 3.18 / 3.94 ± 3.35 / 0.277 / 0.986 / 0.738 / 1.000
rs822391 / 188046505 / 2147 / T/C / 4.01 ± 3.46 / 4 ± 2.88 / 3.77 ± 2.5 / 0.661 / 1.000 / 0.818 / 1.000
rs822396 / 188049579 / 2211 / A/G / 4 ± 3.4 / 3.95 ± 2.88 / 3.7 ± 2.29 / 0.352 / 0.999 / 0.559 / 1.000
rs12495941 / 188050882 / 2120 / G/T / 3.97 ± 3.7 / 4 ± 2.96 / 4 ± 2.76 / 0.090 / 0.731 / 0.267 / 0.985
rs7649121 / 188051487 / 2209 / A/T / 4.01 ± 3.14 / 3.95 ± 3.42 / 3.64 ± 2.88 / 0.186 / 0.938 / 0.432 / 1.000