A Genome-Wide Scan for Childhood Obesity–Associated Traits in French Families Shows Significant Linkage on Chromosome 6q22.31-q23.2
Article Figures & Tables
Figures
- FIG. 1.
Distribution of the age of adiposity rebound in children below (n = 38) or above (n = 207) the 95th percentile. The x-axis gives the age of adiposity rebound. The categories are as follows: 0 included to 2 excluded, 2 included to 3 included, 3 excluded to 5 included, and 5 excluded and more. The y-axis gives the effective in percent.
- FIG. 2.
Results of the multipoint analyses for PCT95, PCT97, PCT99, and AAR. The x-axis gives the chromosome. The y-axis gives the LOD score. MLS LOD scores are given for PCT95, PCT97, and PCT99, and MLB LOD scores are given for AAR.
- FIG. 3.
Results of the MLS (PCT95, PCT97, and PCT99) and MLB (AAR) multipoint analyses after fine-mapping. The y-axis indicates the LOD score. Red, green, and blue curves correspond to PCT95, PCT97, and PCT99 traits, respectively. Black curves correspond to the AAR trait. A Genethon map was used.
Tables
- TABLE 1
Family structures
Number of pedigrees 115 Pedigrees with one sib with BMI ≥95th percentile 18 Pedigrees with two sibs with BMI ≥95th percentile 74 Pedigrees with three sibs with BMI ≥95th percentile 21 Pedigrees with four sibs with BMI ≥95th percentile 2 Number of documented sibpairs 233 Number of sibpairs with BMI ≥95th percentile 149 Number of sibpairs with BMI ≥97th percentile 135 Number of sibpairs with BMI ≥99th percentile 109 - TABLE 2
Phenotypic characteristics by affection status
Phenotypes Children with BMI ≤95th percentile Children with BMI >95th percentile ntotal 47 (boys: 51.1%) 237 (boys: 51.1%) Age (years) 11.91 ± 7.23 (47) 11.89 ± 6.05 (237) BMI (kg/m2) 18.30 ± 4.99 (47) 29.12 ± 13.56 (237) Z score of BMI 0.379 ± 1.47 (47) 3.965 ± 2.57 (237) Age of obesity onset (years) — 4.05 ± 5.27 (219) Age of rebound (years) 5.29 ± 2.86 (38) 2.49 ± 3.25 (207) Data are means ± 95% CI (n).
- TABLE 3
Pearson correlation coefficients between the AAR and the childhood obesity–associated traits PCT95, PCT97, and PCT99
PCT95 PCT97 PCT99 PCT95 — — — PCT97 0.89 — — PCT99 0.76 0.85 — AAR −0.54 −0.53 −0.53 All correlations are significant with a P value <0.001.
- TABLE 4
Markers with evidence for linkage (P ≤ 0.001) in the 10-cM genome scan
Positive markers Interval* Position† (cM) Traits MLB LOD (P)‡ MLS LOD (P)‡ PCORR§ PUNCORR§ 1-LOD unit (CI) (cM) D2S325 2q35 215.26 PCT99 2.77 (0.0002) 3.26 (0.0001) 0.16 0.08 20.83 (222.1–242.9) D6S287 6q22.31 124.49 PCT97 3.61 (0.00002) 4.29 (0.000009) 0.01 0.01 17.03 (128.2–145.2) D6S287 6q22.31 124.49 PCT95 3.08 (0.00008) 3.62 (0.00005) 0.08 0.06 17.03 (128.2–145.2) D6S287 6q22.31 124.49 PCT99 2.07 (0.001) 2.33 (0.001) 0.45 0.37 29.00 (125.3–154.3) D15S1007 15q14 26.78 AAR 2.11 (0.0009) NA 0.73 0.34 17.83 (23.9–41.8) D16S516 16q23.1 112.09 AAR 2.08 (0.001) NA 0.74 0.35 31.43 (87.78–119.21) D19S226 19p13.12 43.34 AAR 2.08 (0.001) NA 0.74 0.35 23.58 (26.2–49.8) - *
* Chromosomes locations were determined from the map available in the Human Genome Browser.
- †
† Haldane’s distances were used to determine the locations of linkage peaks.
- ‡
‡ P: single-test P value;
- §
§ PCORR: empirical genome-wide P value when considering all the traits; PUNCORR: empirical genome-wide P value when considering one trait only. NA, not available. A Genethon map was used.
- *
- TABLE 5
Multipoint results after the fine-mapping step
Chromosome Fine-mapping interval (cM) Average density Trait MLB LOD (P)* MLS LOD (P)* 1-LOD unit (CI) (cM) Location (cM) 2q33.2-q36.3 D2S112-D2S396 3.84 PCT99 2.73 (0.0002) 3.05 (0.0002) 22.34 (214.96–237.30) 230.62 PCT97 2.08 (0.001) 2.33 (0.001) 24.46 (214.00–238.46) 230.62 6q22.31-q23.2 D6S462-D6S441 3.01 PCT97 3.27 (0.00005) 4.06 (0.00002) 10.85 (125.97–136.82) 129.76 PCT95 3.13 (0.00007) 3.77 (0.00003) 11.53 (125.29–136.82) 128.95 15q12-q15.1 D15S128-D15S153 2.22 AAR 2.53 (0.0003) NA 13.67 (21.71–35.38) 32.69 16q22.1-q24.1 D16S415-D16S520 3.13 AAR 2.54 (0.0003) NA 21.68 (95.63–117.31) 105.15 17p13 D17S849-D17S799 1.96 PCT95 2.25 (0.0007) 2.35 (0.001) 6.50 (16.59–23.09) 18.70 19p13.3p13.11 D19S221-D19S414 2.58 AAR 2.13 (0.0009) NA 22.62 (24.71–47.33) 44.60 - *
* P: single-test P value. A Genethon map was used. Only the traits with suggestive evidence for linkage are reported here (LOD MLS ≥2.32, LOD MLB ≥2.08, P ≤ 0.001).
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