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  • Appetite regulation genes are associated with body mass index in black South African adolescents: a genetic association study

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Genetics and genomics
Research
Appetite regulation genes are associated with body mass index in black South African adolescents: a genetic association study
  1. Zané Lombard1,2,
  2. Nigel J Crowther3,
  3. Lize van der Merwe4,5,
  4. Punita Pitamber1,
  5. Shane A Norris6,
  6. Michèle Ramsay1
  1. 1Division of Human Genetics, School of Pathology, Faculty of Health Sciences, National Health Laboratory Service and University of the Witwatersrand, Johannesburg, South Africa
  2. 2Wits Bioinformatics, University of the Witwatersrand, Johannesburg, South Africa
  3. 3Department of Chemical Pathology, School of Pathology, Faculty of Health Sciences, National Health Laboratory Service and University of the Witwatersrand, Johannesburg, South Africa
  4. 4Biostatistics Unit, Medical Research Council, Cape Town, South Africa
  5. 5Department of Statistics, University of Western Cape, Cape Town, South Africa
  6. 6MRC/Wits Developmental Pathways for Health Research Unit, Department of Paediatrics, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
  1. Correspondence to Dr Zané Lombard; zane.lombard{at}wits.ac.za

Abstract

Background Obesity is a complex trait with both environmental and genetic contributors. Genome-wide association studies have identified several variants that are robustly associated with obesity and body mass index (BMI), many of which are found within genes involved in appetite regulation. Currently, genetic association data for obesity are lacking in Africans—a single genome-wide association study and a few replication studies have been published in West Africa, but none have been performed in a South African population.

Objective To assess the association of candidate loci with BMI in black South Africans. The authors focused on single nucleotide polymorphisms (SNPs) in the FTO, LEP, LEPR, MC4R, NPY2R and POMC genes.

Design A genetic association study.

Participants 990 randomly selected individuals from the larger Birth to Twenty cohort (a longitudinal birth cohort study of health and development in Africans).

Measures The authors genotyped 44 SNPs within the six candidate genes that included known BMI-associated SNPs and tagSNPs based on linkage disequilibrium in an African population for FTO, LEP and NPY2R. To assess population substructure, the authors included 18 ancestry informative markers. Weight, height, sex, sex-specific pubertal stage and exact age collected during adolescence (13 years) were used to identify loci that predispose to obesity early in life.

Results Sex, sex-specific pubertal stage and exact age together explain 14.3% of the variation in log(BMI) at age 13. After adjustment for these factors, four SNPs were individually significantly associated with BMI: FTO rs17817449 (p=0.022), LEP rs10954174 (p=0.0004), LEP rs6966536 (p=0.012) and MC4R rs17782313 (p=0.045). Together the four SNPs account for 2.1% of the variation in log(BMI). Each risk allele was associated with an estimated average increase of 2.5% in BMI.

Conclusions The study highlighted SNPs in FTO and MC4R as potential genetic markers of obesity risk in South Africans. The association with two SNPs in the 3′ untranslated region of the LEP gene is novel.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

https://doi.org/10.1136/bmjopen-2012-000873

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    Footnotes

    • To cite: Lombard Z, Crowther NJ, van der Merwe L, et al. Appetite regulation genes are associated with body mass index in black South African adolescents: a genetic association study. BMJ Open 2012;2:e000873. doi:10.1136/bmjopen-2012-000873

    • Contributors SAN, MR, ZL and NJC conceived the idea for the study. SAN provided access to all phenotypic data used in this study. ZL and PP performed the SNP selection and laboratory work. PP completed the STRUCTURE analysis, ZL the Haploview plots and NJC the allelic risk score computation. LvdM performed all other statistical analyses. ZL wrote the first draft of the manuscript, and all authors contributed to, read and approved the final manuscript.

    • Funding This work was supported by the Wellcome Trust (grant number 080535/Z/06/Z to SAN); the South African Medical Research Council and the University of the Witwatersrand for the collection of the samples for the Bt20 cohort and genotyping. In addition, genotyping was funded by the South African National Research Foundation (grant number IFR2011062100004 to MR).

    • Competing interests None.

    • Ethics approval Ethics approval was provided by Human Research Ethics Committee: (Medical) of the University of the Witwatersrand.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement No additional data are available.