Abstract for presentation at 11th International Congress of Human Genetics

Genome-wide linkage scan for QTL influencing infant growth rate: The Fels Longitudinal Study

  • Dr Ellen Demerath, Wright State University Boonshoft School of Medicine, United States
  • Dr Bradford Towne, Wright State University Boonshoft School of Medicine, United States
  • Dr Stefan Czerwinski, Wright State University Boonshoft School of Medicine, United States
  • Dr Audrey Choh, Wright State University Boonshoft School of Medicine, United States
  • Dr Tom Dyer, Southwest Foundation for Biomedical Research, United States
  • Dr Shelley Cole, Southwest Foundation for Biomedical Research, United States
  • Dr John Blangero, Southwest Foundation for Biomedical Research, United States
  • Dr Roger Siervogel, Wright State University Boonshoft School of Medicine, United States

    • Childhood obesity is a serious public health problem worldwide. Given the relative intractability of obesity once it arises, attention should focus on early prevention, and new evidence indicates that rapid early growth is an important predictor of obesity risk. Post-natal growth rate is highly heritable, but little is known of the specific genes influencing patterns of growth in normal infants. In this study, we applied a log-linear function to serial body weight and length measures taken at 1 to 6 month intervals in Fels Longitudinal Study infants followed from 0 to 3 years (N=492). A subset of 286 of these infants has been genotyped for ~400 autosomal markers spanning the genome at ~10 cM intervals. Infant weight, recumbent length, and growth velocities were all highly heritable, with h2 estimates ranging from 0.60 to 0.95. However, the magnitude of additive genetic effects on early growth rate appear to change over the course of infancy, with lower heritability in early infancy, followed by a significant increase in heritability in later infancy. Significant linkage was found for early infant weight velocity (ages 0-6 months) on chromosome 2 at 66 cM (LOD=3.16) and for later infant weight velocity (ages 18 - 36 months) on chromosome 3 at 28 cM (LOD=4.63). Chromosome 12 was found to harbor a QTL influencing infant recumbent length (ages 0-12 months) at 127 cM (LOD=3.33). Suggestive linkage was found on chromosome 6 at 94 cM (LOD=2.84) for birth weight, and on chromosome 11 at 88 cM for weight velocity from 6 weeks to 3 months of age (LOD~2.0-2.3). The QTL at 12q22-23 includes the IGF1 gene, which encodes IGF-1, a key hormonal element in the GH axis, functional concentrations of which are necessary for normal post-natal growth. Future research will focus on identifying additional positional candidate genes underlying normal infant growth. Supported by NIH grants HD36342, HD12252, and MH59490.

    Conference Organiser - ICMS Pty Ltd