TY - JOUR
T1 - Polymorphic Inversions Underlie the Shared Genetic Susceptibility of Obesity-Related Diseases
AU - González, Juan R.
AU - Ruiz-Arenas, Carlos
AU - Cáceres, Alejandro
AU - Morán, Ignasi
AU - López-Sánchez, Marcos
AU - Alonso, Lorena
AU - Tolosana, Ignacio
AU - Guindo-Martínez, Marta
AU - Mercader, Josep M.
AU - Esko, Tonu
AU - Torrents, David
AU - González, Josefa
AU - Pérez-Jurado, Luis A.
N1 - Publisher Copyright:
© 2020 American Society of Human Genetics
PY - 2020/6/4
Y1 - 2020/6/4
N2 - 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 an inversion association analysis 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 for 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.
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 an inversion association analysis 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 for 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.
KW - asthma
KW - common diseases
KW - diabetes
KW - disease co-occurrence
KW - genetic inversions
KW - genomic variation
KW - human traits
KW - hypertension
KW - obesity
KW - obesity-related diseases
UR - https://www.scopus.com/pages/publications/85085621053
U2 - 10.1016/j.ajhg.2020.04.017
DO - 10.1016/j.ajhg.2020.04.017
M3 - Article
C2 - 32470372
AN - SCOPUS:85085621053
SN - 0002-9297
VL - 106
SP - 846
EP - 858
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 6
ER -