An autosomal genome scan for loci influencing longitudinal burden of body mass index from childhood to young adulthood in white sibships: The Bogalusa Heart Study

Abstract

OBJECTIVE:To examine genetic loci linked to a long-term burden and trend of obesity traits, such as body mass index (BMI), from childhood to adulthood. DESIGN: Longitudinal study using serial measurements of BMI from childhood. SUBJECTS: A total of 782 unselected white siblings (representing 521 full and 39 half sib-pairs) from 342 families enrolled in the Bogalusa Heart Study. MEASUREMENTS: A total of 357 microsatellite markers with an average spacing of 9.0 cM spanning the 22 autosomal chromosomes were typed. A quadratic growth curve was developed using a random effects model based on serial measurements of BMI from childhood to adulthood. The serial changes in BMI were measured in terms of long-term burden (area under the curve (AUC) divided by follow-up years) and the long-term trend (incremental AUC, calculated as total AUCÀbaseline AUC). RESULTS: Heritability estimates of long-term measures were 0.78 for total AUC and 0.43 for incremental AUC. In a variancecomponent-based multipoint linkage analysis with SOLAR, linkage to the long-term measures of BMI was observed on chromosomes 1, 5, 7, 12, 13 and 18. For total AUC, LOD scores were 3.0 at 110 cM on chromosome 12, 2.9 at 26 cM and 2.4 at 52 cM on chromosome 7, and 2.2 at 126 cM on chromosome 5. For incremental AUC, LOD scores were 2.9 at 26 cM, 2.1 at 97 cM and 2.3 at 110 cM on chromosome 12, 2.2 at 69 cM on chromosome 7, 2.2 at 91 cM and 2.5 at 150 cM on chromosome 1, 2.0 at 119 cM on chromosome 5, 2.0 at 54 cM on chromosome 13 and 2.0 at 7 cM on chromosome 18. Several important obesity-related candidate genes are located in the regions or near the markers showing positive linkage. CONCLUSION: Linkage evidence found in this study indicates that regions on these chromosomes might harbor genetic loci that affect the propensity to develop obesity from childhood.

Heritability and genetic loci of fatty liver in familial combined hyperlipidemia

“…5), the results for triglycerides did not reach significance by far. Of note, a QTL for BMI has been reported before for the 7p region (37)(38)(39).…”

Anthropometry, Carbohydrate and Lipid Metabolism in the East Flanders Prospective Twin Survey: Linkage of Candidate Genes Using Two Sib-Pair Based Variance Components Analyses

“…Until now, just one genome wide linkage scan reported suggestive linkage with this region (D7S1818; LOD = 2.20) and trends in BMI from childhood to adulthood (Chen et al, 2004). Probably as a consequence, only few association studies with IGFBP1 have been carried out.…”

Assessing, understanding and modifying nutritional status, eating habits and physical activity in European adolescents: The HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) Study

“…Significant and suggestive linkage with long-term burden and trend of body mass index was observed on chromosomes 1, 5, 7, 12, 13 and 18. Candidate genes involved in the pathophysiology of obesity are identified in all regions on six chromosomes except for 7q11.1 82 . Some individuals appear to be relatively sensitive to dietary or lifestyle intervention, whereas others are quite insensitive.…”