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Genome-wide scan for adiposity-related phenotypes in adults from American Samoa

International Journal of Obesity volume 31, pages 1832–1842 (2007)Cite this article

Abstract

Objective:

To detect quantitative trait loci influencing adiposity-related phenotypes assessed by body mass index (BMI), abdominal circumference (ABDCIR), percent body fat (%BFAT) and fasting serum leptin and adiponectin using a whole genome linkage scan of families from American Samoa.

Design:

Family-based linkage analysis, the probands and family members were unselected for obesity.

Subjects:

A total of 583 phenotyped American Samoan adults, of which 578 were genotyped in 34 pedigrees.

Measurements:

A total of 377 autosomal and 18 X chromosome microsatellite markers were typed at an approximate average spacing of 10 cM spanning the genome. Multipoint LOD (logarithm of the odds) scores were calculated using variance-components approaches and SOLAR/LOKI software. The covariates simultaneously evaluated were age, sex, education, farm work and cigarette smoking, with a significance level of 0.1. Due to the stochastic nature of LOKI, we report the average of maximum LOD scores from 10 runs.

Results:

Significant linkage to leptin was found at 6q32.2 with LOD of 3.83. Suggestive linkage to leptin was found at 16q21:LOD=2.98, 1q42.2:LOD=1.97, 5q11.2:LOD=2.08, 12q24.23:LOD=2.00, 19p13.3:LOD=2.05; adiponectin was linked to 13q33.1–q22.1:LOD=2.41; %BFAT was linked to 16q12.2–q21, LOD=2.24; ABDCIR was linked to 16q23.1:LOD=1.95; %BFAT-adjusted leptin to 14q12, LOD=2.01; %BFAT-adjusted ABDCIR to 1q31.1, LOD=2.36, to 3q27.3–q28, LOD=2.10 and to 12p12.3, LOD=2.04.

Conclusion:

We found strong evidence for a major locus on 6q23.2 influencing serum leptin levels in American Samoans. The 16q21 region appears to harbor a susceptibility locus that has significant pleiotrophic effects on phenotypes BMI, %BFAT, leptin and ABDCIR as shown by bivariate linkage analyses. Several other loci of varying significance were detected across the genome.

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Acknowledgements

Our work is supported by NIH grant R01-DK59642 (ST M, PI). Karolina Åberg was supported by The American Scandinavia Foundation and by The Knut and Alice Wallenberg's fund. We thank the fieldwork team of students and local assistants for their hard work in American Samoa in 2002. We thank the leaders of the American Samoa Department of Health for their support and the local political officials for their permission to work in the villages. We are grateful to the families and study participants for their contributions to this research.

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Authors and Affiliations

  1. Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    F Dai & D E Weeks

  2. Department of Community Health and Anthropology, International Health Institute, Brown University, Providence, RI, USA

    E D Keighley, S T Roberts & S T McGarvey

  3. Department of Environmental Health, Center for Genome Information, University of Cincinnati, Cincinnati, OH, USA

    G Sun, S R Indugula, D Smelser, L Jin & R Deka

  4. Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    K Åberg & D E Weeks

  5. Tafuna Family Health Center, Pago Pago, American Samoa, USA

    J Tuitele

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  1. F Dai
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Correspondence to S T McGarvey.

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Authors' contributions FD, under the supervision of DEW, carried out the primary statistical analyses of the data and wrote much of the manuscript. EDK, under the supervision of STM, performed all phenotype data management and checking and correction of the reported pedigrees. GS, SRI and DS, under the supervision of RD, performed DNA extraction, genotyping of all markers, data cleaning and transfer of data to the laboratory of DEW. STR, under the supervision of STM, was field director, and performed initial data management of phenotypic and pedigree data. KÅ, under the supervision of DEW, reanalyzed the data independently, and so provided valuable double checks that our analyses were done correctly. JT provided guidance in conduct of the fieldwork. RD and LJ participated in the designing the molecular work, quality control, data-management and supervised the analysis of the raw genotyping data. STM, RD and DEW collaboratively designed and led this study and obtained funding for it. All the authors read and approved the final manuscript.

Supplementary information accompanies the paper on International Journal of Obesity web site (http://www.nature.com/ijo)

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Dai, F., Keighley, E., Sun, G. et al. Genome-wide scan for adiposity-related phenotypes in adults from American Samoa. Int J Obes 31, 1832–1842 (2007). https://doi.org/10.1038/sj.ijo.0803675

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