European Journal of Human Genetics (2009) 17, 258–266; doi:10.1038/ejhg.2008.152; published online 10 September 2008

Genome-wide linkage screen for stature and body mass index in 3.032 families: evidence for sex- and population-specific genetic effects

Sampo Sammalisto1, Tero Hiekkalinna1,2, Karen Schwander3, Sharon Kardia4, Alan B Weder5, Beatriz L Rodriguez6, Alessandro Doria7, Jennifer A Kelly8, Gail R Bruner8, John B Harley8, Susan Redline9, Emma K Larkin9, Sanjay R Patel10, Amy JH Ewan11, James L Weber11, Markus Perola1,2 and Leena Peltonen1,2,12

  1. 1Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland
  2. 2Department of Medical Genetics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
  3. 3Division of Biostatistics, Washington University School of Medicine, St Louis, MO, USA
  4. 4Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA
  5. 5Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, MI, USA
  6. 6Pacific Health Research Institute, Honolulu, HI, USA
  7. 7Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
  8. 8Oklahoma Medical Research Foundation, Arthritis and Immunology, Oklahoma City, OK, USA
  9. 9Center for Clinical Investigation, School of Medicine, Case Western Reserve University, Cleveland, OH, USA
  10. 10Division of Pulmonary Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA
  11. 11Marshfield Clinic Research Foundation, Marshfield, WI, USA
  12. 12The Broad Institute, MIT, Boston, MA, USA

Correspondence: Professor L Peltonen, Department of Medical Genetics, University of Helsinki, National Public Health Institute, Biomedicum, Haartmaninkatu 8, Helsinki, FIN 00251, Finland. Tel: +358 9 4744 8393; Fax: +358 9 4744 8480; E-mail:

Received 30 October 2007; Revised 1 July 2008; Accepted 16 July 2008; Published online 10 September 2008.



Stature (adult body height) and body mass index (BMI) have a strong genetic component explaining observed variation in human populations; however, identifying those genetic components has been extremely challenging. It seems obvious that sample size is a critical determinant for successful identification of quantitative trait loci (QTL) that underlie the genetic architecture of these polygenic traits. The inherent shared environment and known genetic relationships in family studies provide clear advantages for gene mapping over studies utilizing unrelated individuals. To these ends, we combined the genotype and phenotype data from four previously performed family-based genome-wide screens resulting in a sample of 9.371 individuals from 3.032 African-American and European-American families and performed variance-components linkage analyses for stature and BMI. To our knowledge, this study represents the single largest family-based genome-wide linkage scan published for stature and BMI to date. This large study sample allowed us to pursue population- and sex-specific analyses as well. For stature, we found evidence for linkage in previously reported loci on 11q23, 12q12, 15q25 and 18q23, as well as 15q26 and 19q13, which have not been linked to stature previously. For BMI, we found evidence for two loci: one on 7q35 and another on 11q22, both of which have been previously linked to BMI in multiple populations. Our results show both the benefit of (1) combining data to maximize the sample size and (2) minimizing heterogeneity by analyzing subgroups where within-group variation can be reduced and suggest that the latter may be a more successful approach in genetic mapping.


body height, body mass index, linkage mapping, quantitative trait loci