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Genome-wide linkage and peak-wide association study of obesity-related quantitative traits in Caribbean Hispanics

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Abstract

Although obesity is more prevalent in Hispanics than non-Hispanic whites in the United States, little is known about the genetic etiology of the related traits in this population. To identify genetic loci influencing obesity in non-Mexican Hispanics, we performed a genome-wide linkage scan in 1,390 subjects from 100 Caribbean Hispanic families on six obesity-related quantitative traits: body mass index (BMI), body weight, waist circumference, waist-to-hip ratio, abdominal and average triceps skinfold thickness after adjusting for significant demographic and lifestyle factors. We then carried out an association analysis of the linkage peaks and the FTO gene in an independent community-based Hispanic subcohort (N = 652, 64% Caribbean Hispanics) from the Northern Manhattan Study. Evidence of linkage was strongest on 1q43 with multipoint LOD score of 2.45 (p = 0.0004) for body weight. Suggestive linkage evidence of LOD > 2.0 was also identified on 1q43 for BMI (LOD = 2.03), 14q32 for abdominal skinfold thickness (LOD = 2.17), 16p12 for BMI (LOD = 2.27) and weight (LOD = 2.26), and 16q23–24 for average triceps skinfold thickness (LOD = 2.32). In the association analysis of 6,440 single nucleotide polymorphisms (SNPs) under 1-LOD unit down regions of our linkage peaks on chromosome 1q43 and 16p12 as well as in the FTO gene, we found that two SNPs (rs6665519 and rs669231) on 1q43 and one FTO SNP (rs12447427) were significantly associated with BMI or body weight after adjustment for multiple testing. Our results suggest that in addition to FTO, multiple genetic loci, particularly those on 1q43 region, may contribute to the variations in obesity-related quantitative traits in Caribbean Hispanics.

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Acknowledgments

This work was supported by the National Institute of Neurologic Disorders and Stroke [R01NS40807 to R.L.S., R01NS047655 and K24 NS 062737 to T.R., R37NS29993 to R.L.S]; and Evelyn F. McKnight Center for Age-related Memory Loss. We are thankful to the study participants for their collaboration and to all staff of the Northern Manhattan Study and Family Study for their energetic efforts to this study, and in particular Edison Sabala and Janet DeRosa.

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Authors and Affiliations

  1. Department of Neurology, Miller School of Medicine, University of Miami, Miami, 1120 NW 14th Street, FL, 33136, USA

    Chuanhui Dong, Mark S. McClendon, Tatjana Rundek & Ralph L. Sacco

  2. John T. McDonald Department of Human Genetics, John P Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA

    Ashley Beecham, Susan Slifer, Liyong Wang, Susan H. Blanton & Ralph L. Sacco

  3. Department of Epidemiology and Public Health, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA

    Ralph L. Sacco

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  1. Chuanhui Dong
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  2. Ashley Beecham
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  3. Susan Slifer
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  8. Ralph L. Sacco
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Correspondence to Ralph L. Sacco.

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Dong, C., Beecham, A., Slifer, S. et al. Genome-wide linkage and peak-wide association study of obesity-related quantitative traits in Caribbean Hispanics. Hum Genet 129, 209–219 (2011). https://doi.org/10.1007/s00439-010-0916-2

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