Polymorphic Inversions Underlie the Shared Genetic Susceptibility of Obesity-Related Diseases

被引：12

作者：

Gonzalez, Juan R. ^{[1
,2
,3
,4
]}

Ruiz-Arenas, Carlos ^{[1
,2
]}

Caceres, Alejandro ^{[1
,2
,3
]}

Moran, Ignasi ^{[5
]}

Lopez-Sanchez, Marcos ^{[6
,7
]}

Alonso, Lorena ^{[5
]}

Tolosana, Ignacio ^{[1
]}

Guindo-Martinez, Marta ^{[5
]}

Mercader, Josep M. ^{[5
,8
,9
,10
,11
]}

Esko, Tonu ^{[12
,13
]}

Torrents, David ^{[5
,14
]}

Gonzalez, Josefa ^{[15
]}

Perez-Jurado, Luis A. ^{[2
,6
,7
,16
,17
]}

机构：

[1] Barcelona Inst Global Hlth ISGlobal, Barcelona 08003, Spain

[2] IMIM Hosp Mar Res Inst, Barcelona 08003, Spain

[3] Ctr Invest Biomed Red Epidemiol & Salud Publ CIBE, Barcelona 08003, Spain

[4] Univ Autonoma Barcelona UAB, Dept Math, Barcelona 08193, Spain

[5] Barcelona Supercomp Ctr BSC CNS, Joint BSC CRG IRB Res Program Computat Biol, Barcelona 08034, Spain

[6] Univ Pompeu Fabra, Dept Expt & Hlth Sci CEXS, Barcelona 08003, Spain

[7] Ctr Invest Biomed Red Enfermedades Raras CIBERER, Barcelona 08003, Spain

[8] Broad Inst Harvard & MIT, Programs Metab & Med & Populat Genet, Cambridge, MA 02142 USA

[9] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA

[10] Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA

[11] Harvard Med Sch, Dept Med, Boston, MA 02115 USA

[12] Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia

[13] Univ Tartu, Inst Mol & Cell Biol, EE-51010 Tartu, Estonia

[14] Inst Catalana Recerca & Estudis Avancats ICREA, Barcelona 08003, Spain

[15] Univ Pompeu Fabra, Inst Evolutionary Biol, CSIC, Barcelona 08003, Spain

[16] South Australian Hlth & Med Res Inst, Womens & Childrens Hosp, Adelaide, SA 5005, Australia

[17] Univ Adelaide, Adelaide, SA 5005, Australia

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2020年 / 106卷 / 06期

基金：

欧盟地平线“2020”; 美国国家卫生研究院;

关键词：

VARIANTS; ASSOCIATION; COUNTRIES; INSIGHTS;

D O I：

10.1016/j.ajhg.2020.04.017

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：846 / 858

页数：13

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