Possible genomic imprinting of three human obesity-related genetic loci

Abstract

To detect potentially imprinted, obesity-related genetic loci, we performed genomewide parent-of-origin linkage analyses under an allele-sharing model for discrete traits and under a family regression model for obesity-related quantitative traits, using a European American sample of 1,297 individuals from 260 families, with 391 microsatellite markers. We also used two smaller, independent samples for replication (a sample of 370 German individuals from 89 families and a sample of 277 African American individuals from 52 families). For discrete-trait analysis, we found evidence for a maternal effect in chromosome region 10p12 across the three samples, with LOD scores of 5.69 (single-point) and 4.52 (multipoint) for the pooled sample. For quantitative-trait analysis, we found the strongest evidence for a maternal effect (single-point LOD of 2.85; multipoint LOD of 4.01 for body mass index [BMI] and 3.69 for waist circumference) in region 12q24 and for a paternal effect (single-point LOD of 4.79; multipoint LOD of 3.72 for BMI) in region 13q32, in the European American sample. The results suggest that parent-of-origin effects, perhaps including genomic imprinting, may play a role in human obesity.

Figure 1

Results of genomewide parent-of-origin analyses for discrete traits (BMI⩾27 and BMI⩾30) in the EA sample. The Y-axis presents multipoint LOD scores, with consideration of only maternal transmission (red line) and only paternal transmission (blue line). Chromosome numbers are indicated above each graph.

Figure 2

Results of genomewide parent-of-origin analyses for quantitative traits (BMI, waist circumference, and %fat) in the EA sample. The Y-axis presents multipoint LOD scores, with consideration of only maternal transmission (red line) and only paternal transmission (blue line). Chromosome numbers are indicated above each graph.

Figure 3

Results for chromosomes 12 and 13 for quantitative traits (BMI, waist circumference, and %fat) in the EA sample. The Y-axis presents multipoint LOD scores, with consideration of only maternal transmission (red line) and only paternal transmission (blue line).

Figure 4

Results for chromosome 10 in analyses of discrete traits (BMI⩾27 in the EA and AA samples; BMI ⩾90th percentile in the MB sample) in the individual and combined samples, by use of ALLEGRO and ASPEX. The Y-axis presents multipoint LOD scores, with consideration of only maternal transmission (red line) and only paternal transmission (blue line).