A Genomewide Linkage Scan for Abdominal Subcutaneous and Visceral Fat in Black and White Families
The HERITAGE Family Study
- Treva Rice1,
- Yvon C. Chagnon4,
- Louis Pérusse5,
- Ingrid B. Borecki12,
- Olavi Ukkola78,
- Tuomo Rankinen8,
- Jacques Gagnon6,
- Arthur S. Leon9,
- James S. Skinner10,
- Jack H. Wilmore11,
- Claude Bouchard8 and
- D.C. Rao123
- 1Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri
- 2Department of Genetics, Washington University School of Medicine, St. Louis, Missouri
- 3Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri
- 4Physical Activity Sciences Laboratory, Laval University, Québec, Canada
- 5Division of Kinesiology and Department of Preventive Medicine, Laval University, Québec, Canada
- 6Molecular Endocrinology Laboratory, Laval University, Québec, Canada
- 7Department of Internal Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland
- 8Pennington Biomedical Research Center, Baton Rouge, LA
- 9School of Kinesiology and Leisure Studies, University of Minnesota, Minneapolis, Minnesota
- 10Division of Kinesiology, Indiana University, Bloomington, Indiana
- 11Department of Health and Kinesiology, Texas A & M University, College Station, Texas
Abstract
Abdominal visceral fat (AVF), abdominal subcutaneous fat (ASF), and abdominal total fat (ATF) were measured using a computed tomography scan, both before (baseline) and after (post) a 20-week endurance exercise training protocol in the HERITAGE Family Study. Each of the baseline and response (post minus baseline) measures was adjusted for several covariates, including total fat mass, and responses to training were further adjusted for baseline levels. Multipoint variance components linkage analysis using a genomewide scan of 344 markers was conducted separately by race using race-specific allele frequencies. Several promising results (P < 0.0023) were obtained. For baseline AVF, the best evidence was on 2q22.1 and 2q33.2-q36.3 (including the IRS1 locus) in whites, with suggestive findings on 7q22.2-q31.3 (including the LEP locus) in blacks. Although several regions were indicated for baseline ASF, only 4q31.22-q32.2 and 11p15.4-p11.2 replicated the results of another study. For responses to training, promising results were limited to ASF and ATF primarily on 7q36.2 (including NOS3) in blacks, with suggestive regions (P < 0.01) on 1q21.2-q24.1 (S100A, ATP1A2, and ATP1B1), 10q25.2 (ADRA2A), and 11p15.5 (IGF2). In summary, the 4q and 11p regions have now been implicated in two independent studies for ASF; further research is warranted to identify the genes and mutations in these regions that are responsible for fat accumulation in the abdominal depot. Additional work in an independent sample is needed to verify the linkages for baseline AVF as well as the response measures.
Footnotes
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Address correspondence and reprint requests to Treva Rice, Ph.D., Division of Biostatistics, Washington University School of Medicine, 660 S. Euclid Ave., Box 8067, St. Louis, MO 63110. E-mail: treva{at}wubios.wustl.edu.
Received for publication 26 September 2001 and accepted in revised form 5 December 2001.
AVF, abdominal visceral fat; ASF, abdominal subcutaneous fat; ATF, abdominal total fat; CT, computed axial tomography; FM, total body fat mass; h2g, locus-specific heritability; h2r, residual heritability; LOD, logarithm of odds; LRT, likelihood ratio test; QFS, Québec Family Study; QTL, quantitative trait locus.
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