Abstract
Common variants near melanocortin 4 receptor (MC4R) gene are shown to be associated with adiposity but have varied effects in different age groups. Among Indians, studies have shown association of these variants with obesity in adults, but their association in children is yet to be confirmed. We evaluated association of rs17782313 and rs12970134 near MC4R with adiposity and related traits in Indians including 1362 children and 4077 adults (consisting of 2049 diabetic and 2028 nondiabetic adult subjects). Both variants rs17782313 and rs12970134 showed strong association with adiposity measures (weight, body mass index and waist circumference) in children (P-range 7.6 × 10–5–3.8 × 10–12) and nominal association in nondiabetic adults (P-range 0.05–0.003). Effect sizes on adiposity measures in children (β range 0.22–0.26 Z-score) were ∼3-fold higher compared with adults (β range 0.06–0.08). The minor alleles of both variants showed borderline association (P-range 0.08–0.04) with risk of type 2 diabetes in adults. Meta-analysis of rs12970134 in >12 000 Indian adults corroborated its association with adiposity (P⩽2.2 × 10–9), homeostasis model assessment-estimated insulin resistance (P=4.0 × 10–5) and type 2 diabetes (P=0.003) with only moderate heterogeneity, suggesting similar effect on adult Indians residing in different geographical regions. In conclusion, the study demonstrates association of variants near MC4R with obesity and related traits in Indian children and adults, with higher impact during childhood.
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Acknowledgements
We are thankful to all the participants of the study. We are grateful to the parents of participating children and their school authorities for support and cooperation. We thank Mr Kuntal Bhadra from the Institute of Nuclear Medicine and Allied Sciences for his help in sample collection. We thank Dr Abhay Sharma and Dr Anurag Agrawal from Council of Scientific and Industrial Research (CSIR)—Institute of Genomics and Integrative Biology for their critical evaluation of the manuscript. This study was supported by ‘Diabetes mellitus-New drug discovery R&D, molecular mechanisms and genetic and epidemiological factors’ (NWP0032-OB3) funded by CSIR, Government of India. RT is grateful to the Fogarty International Center and the Eunice Kennedy Shriver National Institute Of Child Health and Human Development at the National Institutes of Health for providing post doctoral fellowship from the grant number 1 D43 HD065249.
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Prakash Dwivedi, O., Tabassum, R., Chauhan, G. et al. Strong influence of variants near MC4R on adiposity in children and adults: a cross-sectional study in Indian population. J Hum Genet 58, 27–32 (2013). https://doi.org/10.1038/jhg.2012.129
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DOI: https://doi.org/10.1038/jhg.2012.129
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