RT Journal Article
SR Electronic
T1 Polymorphic inversions underlie the shared genetic susceptibility to prevalent common diseases
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 859280
DO 10.1101/859280
A1 Juan R González
A1 Carlos Ruiz-Arenas
A1 Alejandro Cáceres
A1 Ignasi Morán
A1 Marcos López
A1 Lorena Alonso
A1 Ignacio Tolosana
A1 Marta Guindo-Martínez
A1 Josep M Mercader
A1 Tonu Esko
A1 David Torrents
A1 Josefa González
A1 Luis A Pérez-Jurado
YR 2019
UL http://biorxiv.org/content/early/2019/11/29/859280.abstract
AB The burden of several common diseases including obesity, diabetes, hypertension, asthma, and depression is increasing in most world populations. However, the mechanisms underlying the numerous epidemiological and genetic correlations among these disorders remain largely unknown. We investigated whether common polymorphic inversions underlie the shared genetic influence of these disorders. We performed the largest inversion association analysis to date, including 21 inversions and 25 obesity-related traits, on a total of 408,898 Europeans, and validated the results in 67,299 independent individuals. Seven inversions were associated with multiple diseases while inversions at 8p23.1, 16p11.2 and 11q13.2 were strongly associated with the co-occurrence of obesity with other common diseases. Transcriptome analysis across numerous tissues revealed strong candidate genes of obesity-related traits. Analyses in human pancreatic islets indicated the potential mechanism of inversions in the susceptibility of diabetes by disrupting the cis-regulatory effect of SNPs from their target genes. Our data underscore the role of inversions as major genetic contributors to the joint susceptibility to common complex diseases.