Following the footprints of polymorphic inversions on SNP data : from detection to association tests
Cáceres, Alejandro (Centre de Recerca en Epidemiologia Ambiental)
González, Juan Ramón (Universitat Autònoma de Barcelona. Departament de Matemàtiques)

Data:	2015
Resum:	Inversion polymorphisms have important phenotypic and evolutionary consequences in humans. Two different methodologies have been used to infer inversions from SNP dense data, enabling the use of large cohorts for their study. One approach relies on the differences in linkage disequilibrium across breakpoints; the other one captures the internal haplotype groups that tag the inversion status of chromosomes. In this article, we assessed the convergence of the two methods in the detection of 20 human inversions that have been reported in the literature. The methods converged in four inversions including inv-8p23, for which we studied its association with low-BMI in American children. Using a novel haplotype tagging method with control on inversion ancestry, we computed the frequency of inv-8p23 in two American cohorts and observed inversion haplotype admixture. Accounting for haplotype ancestry, we found that the European inverted allele in children carries a recessive risk of underweight, validated in an independent Spanish cohort (combined: OR= 2. 00, P = 0. 001). While the footprints of inversions on SNP data are complex, we show that systematic analyses, such as convergence of different methods and controlling for ancestry, can reveal the contribution of inversions to the ancestral composition of populations and to the heritability of human disease.
Ajuts:	European Commission 201413 Ministerio de Ciencia e Innovación MTM2011-26515 Ministerio de Ciencia e Innovación MTM2010-09526-E Ministerio de Ciencia e Innovación SAF2008-00357 Instituto de Salud Carlos III CB06/02/0041 Instituto de Salud Carlos III FISPI041436 Instituto de Salud Carlos III PI081151 Instituto de Salud Carlos III PI041705 Instituto de Salud Carlos III PS09/00432 Agència de Gestió d'Ajuts Universitaris i de Recerca 1999/SGR-00241
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Computational methods ; Genomics
Publicat a:	Nucleic acids research, Vol. 43, issue 8 (April 2015) , e53, ISSN 1362-4962

DOI: 10.1093/nar/gkv073
PMID: 25672393

11 p, 3.5 MB

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