Article Dans Une Revue American Journal of Human Genetics Année : 2014

A Common 16p11.2 Inversion Underlies the Joint Susceptibility to Asthma and Obesity

1 Center for Research in Environmental Epidemiology (CREAL), Barcelona 08003, Spain; Hospital del Mar Research Institute (IMIM), Barcelona 08003, Spain; Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública (CIBERESP), Barcelona 08003, Spain; Department of Mathematics, Universitat Autònoma de Barcelona, Bellaterra (Barcelona) 08193
2 Center for Research in Environmental Epidemiology (CREAL), Barcelona 08003, Spain; Hospital del Mar Research Institute (IMIM), Barcelona 08003
3 Tartu Ülikool = University of Tartu [Estonie]
4 UPF - Universitat Pompeu Fabra [Barcelona]
5 Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra (Barcelona) 08193
6 Center for Research in Environmental Epidemiology (CREAL), Barcelona 08003, Spain; Hospital del Mar Research Institute (IMIM), Barcelona 08003, Spain; Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública (CIBERESP), Barcelona 08003
7 Equipe avenir "Environmental Epidemiology Applied to Fecundity and Reproduction"
8 U946 - Variabilité Génétique et Maladies Humaines
9 IFR105 - IUH - IFR de Saint-Louis - Institut universitaire d'hématologie
10 CESP - Centre de recherche en épidémiologie et santé des populations
11 Center for Research in Environmental Epidemiology (CREAL), Barcelona 08003, Spain; Hospital del Mar Research Institute (IMIM), Barcelona 08003, Spain; Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública (CIBERESP), Barcelona 08003, Spain; Genes and Disease Group, Centre for Genomic Regulation (CRG), Barcelona 08003
12 National Heart and Lung Institute, Imperial College, London SW7 2AZ
13 IMIM-Hospital del Mar
14 EMU - Estonian University of Life Sciences
15 ICREA and ICTA
Mario Cáceres
  • Fonction : Auteur

Résumé

The prevalence of asthma and obesity is increasing worldwide, and obesity is a well-documented risk factor for asthma. The mechanisms underlying this association and parallel time trends remain largely unknown but genetic factors may be involved. Here, we report on a common ~0.45 Mb genomic inversion at 16p11.2 that can be accurately genotyped via SNP array data. We show that the inversion allele protects against the joint occurrence of asthma and obesity in five large independent studies (combined sample size of 317 cases and 543 controls drawn from a total of 5,809 samples; combined OR ¼ 0.48, p ¼ 5.5 3 10 À6). Allele frequencies show remarkable worldwide population stratification, ranging from 10% in East Africa to 49% in Northern Europe, consistent with discordant and extreme genetic drifts or adaptive selections after human migration out of Africa. Inversion alleles strongly correlate with expression levels of neighboring genes, especially TUFM (p ¼ 3.0 3 10 À40) that encodes a mitochondrial protein regulator of energy balance and inhibitor of type 1 interferon, and other candidates for asthma (IL27) and obesity (APOB48R and SH2B1). Therefore, by affecting gene expression, the ~0.45 Mb 16p11.2 inversion provides a genetic basis for the joint susceptibility to asthma and obesity, with a population attributable risk of 39.7%. Differential mitochondrial function and basal energy balance of inversion alleles might also underlie the potential selection signature that led to their uneven distribution in world populations.

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Dates et versions

hal-04315107 , version 1 (30-11-2023)

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Juan R González, Alejandro Cáceres, Tonu Esko, Ivon Cuscó, Marta Puig, et al.. A Common 16p11.2 Inversion Underlies the Joint Susceptibility to Asthma and Obesity. American Journal of Human Genetics, 2014, 94 (3), pp.361 - 372. ⟨10.1016/j.ajhg.2014.01.015⟩. ⟨hal-04315107⟩
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