Polymorphic Inversions Underlie the Shared Genetic Susceptibility of Obesity-Related Diseases.
Adolescent
Adult
Aged
Aged, 80 and over
Alleles
Chromosome Inversion
/ genetics
Chromosomes, Human, Pair 16
/ genetics
Chromosomes, Human, Pair 8
/ genetics
Datasets as Topic
/ standards
Diabetes Mellitus
/ genetics
Europe
/ ethnology
Female
Gene Expression Profiling
Genetic Predisposition to Disease
Haplotypes
Humans
Hypertension
/ complications
Islets of Langerhans
/ metabolism
Male
Middle Aged
Obesity
/ complications
Polymorphism, Genetic
Polymorphism, Single Nucleotide
/ genetics
Reproducibility of Results
Young Adult
asthma
common diseases
diabetes
disease co-occurrence
genetic inversions
genomic variation
human traits
hypertension
obesity
obesity-related diseases
Journal
American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475
Informations de publication
Date de publication:
04 06 2020
04 06 2020
Historique:
received:
07
01
2020
accepted:
28
04
2020
pubmed:
30
5
2020
medline:
9
10
2020
entrez:
30
5
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32470372
pii: S0002-9297(20)30126-9
doi: 10.1016/j.ajhg.2020.04.017
pmc: PMC7273535
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
846-858Informations de copyright
Copyright © 2020 American Society of Human Genetics. All rights reserved.
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