Variants in ABCG8 and TRAF3 genes confer risk for gallstone disease in admixed Latinos with Mapuche Native American ancestry

Bernabé I. Bustos, Eduardo Pérez-Palma, Stephan Buch, Lorena Azócar, Eleodoro Riveras, Giorgia D. Ugarte, Mohammad Toliat, Peter Nürnberg, Wolfgang Lieb, Andre Franke, Sebastian Hinz, Greta Burmeister, Witigo von Schönfels, Clemens Schafmayer, Henry Völzke, Uwe Völker, Georg Homuth, Markus M. Lerch, José Luis Santos, Klaus PuschelClaudia Bambs, Juan Carlos Roa, Rodrigo A. Gutiérrez, Jochen Hampe, Giancarlo V. De Ferrari, Juan Francisco Miquel

Resultado de la investigación: Article

2 Citas (Scopus)

Resumen

Latin Americans and Chilean Amerindians have the highest prevalence of gallstone disease (GSD) and gallbladder cancer (GBC) in the world. A handful of loci have been associated with GSD in populations of predominantly European ancestry, however, they only explain a small portion of the genetic component of the disease. Here, we performed a genome-wide association study (GWAS) for GSD in 1,095 admixed Chilean Latinos with Mapuche Native American ancestry. Disease status was assessed by cholecystectomy or abdominal ultrasonography. Top-10 candidate variants surpassing the suggestive cutoff of P < 1 × 10 −5 in the discovery cohort were genotyped in an independent replication sample composed of 1,643 individuals. Variants with positive replication were further examined in two European GSD populations and a Chilean GBC cohort. We consistently replicated the association of ABCG8 gene with GSD (rs11887534, P = 3.24 × 10 −8 , OR = 1.74) and identified TRAF3 (rs12882491, P = 1.11 × 10 −7 , OR = 1.40) as a novel candidate gene for the disease in admixed Chilean Latinos. ABCG8 and TRAF3 variants also conferred risk to GBC. Gene expression analyses indicated that TRAF3 was significantly decreased in gallbladder (P = 0.015) and duodenal mucosa (P = 0.001) of GSD individuals compared to healthy controls, where according to GTEx data in the small intestine, the presence of the risk allele contributes to the observed effect. We conclude that ABCG8 and TRAF3 genes are associated with GSD and GBC in admixed Latinos and that decreased TRAF3 levels could enhance gallbladder inflammation as is observed in GSD and GSD-associated GBC.

Idioma originalEnglish
Número de artículo772
PublicaciónScientific Reports
Volumen9
N.º1
DOI
EstadoPublished - 28 ene 2019

Huella dactilar

TNF Receptor-Associated Factor 3
North American Indians
Gallstones
Hispanic Americans
Gallbladder Neoplasms
Genes
Inborn Genetic Diseases
Cholecystitis
Genome-Wide Association Study
Cholecystectomy
Gallbladder
Population
Small Intestine

ASJC Scopus subject areas

  • General

Citar esto

Bustos, B. I., Pérez-Palma, E., Buch, S., Azócar, L., Riveras, E., Ugarte, G. D., ... Miquel, J. F. (2019). Variants in ABCG8 and TRAF3 genes confer risk for gallstone disease in admixed Latinos with Mapuche Native American ancestry. Scientific Reports, 9(1), [772]. https://doi.org/10.1038/s41598-018-35852-z
Bustos, Bernabé I. ; Pérez-Palma, Eduardo ; Buch, Stephan ; Azócar, Lorena ; Riveras, Eleodoro ; Ugarte, Giorgia D. ; Toliat, Mohammad ; Nürnberg, Peter ; Lieb, Wolfgang ; Franke, Andre ; Hinz, Sebastian ; Burmeister, Greta ; von Schönfels, Witigo ; Schafmayer, Clemens ; Völzke, Henry ; Völker, Uwe ; Homuth, Georg ; Lerch, Markus M. ; Santos, José Luis ; Puschel, Klaus ; Bambs, Claudia ; Roa, Juan Carlos ; Gutiérrez, Rodrigo A. ; Hampe, Jochen ; De Ferrari, Giancarlo V. ; Miquel, Juan Francisco. / Variants in ABCG8 and TRAF3 genes confer risk for gallstone disease in admixed Latinos with Mapuche Native American ancestry. En: Scientific Reports. 2019 ; Vol. 9, N.º 1.
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title = "Variants in ABCG8 and TRAF3 genes confer risk for gallstone disease in admixed Latinos with Mapuche Native American ancestry",
abstract = "Latin Americans and Chilean Amerindians have the highest prevalence of gallstone disease (GSD) and gallbladder cancer (GBC) in the world. A handful of loci have been associated with GSD in populations of predominantly European ancestry, however, they only explain a small portion of the genetic component of the disease. Here, we performed a genome-wide association study (GWAS) for GSD in 1,095 admixed Chilean Latinos with Mapuche Native American ancestry. Disease status was assessed by cholecystectomy or abdominal ultrasonography. Top-10 candidate variants surpassing the suggestive cutoff of P < 1 × 10 −5 in the discovery cohort were genotyped in an independent replication sample composed of 1,643 individuals. Variants with positive replication were further examined in two European GSD populations and a Chilean GBC cohort. We consistently replicated the association of ABCG8 gene with GSD (rs11887534, P = 3.24 × 10 −8 , OR = 1.74) and identified TRAF3 (rs12882491, P = 1.11 × 10 −7 , OR = 1.40) as a novel candidate gene for the disease in admixed Chilean Latinos. ABCG8 and TRAF3 variants also conferred risk to GBC. Gene expression analyses indicated that TRAF3 was significantly decreased in gallbladder (P = 0.015) and duodenal mucosa (P = 0.001) of GSD individuals compared to healthy controls, where according to GTEx data in the small intestine, the presence of the risk allele contributes to the observed effect. We conclude that ABCG8 and TRAF3 genes are associated with GSD and GBC in admixed Latinos and that decreased TRAF3 levels could enhance gallbladder inflammation as is observed in GSD and GSD-associated GBC.",
author = "Bustos, {Bernab{\'e} I.} and Eduardo P{\'e}rez-Palma and Stephan Buch and Lorena Az{\'o}car and Eleodoro Riveras and Ugarte, {Giorgia D.} and Mohammad Toliat and Peter N{\"u}rnberg and Wolfgang Lieb and Andre Franke and Sebastian Hinz and Greta Burmeister and {von Sch{\"o}nfels}, Witigo and Clemens Schafmayer and Henry V{\"o}lzke and Uwe V{\"o}lker and Georg Homuth and Lerch, {Markus M.} and Santos, {Jos{\'e} Luis} and Klaus Puschel and Claudia Bambs and Roa, {Juan Carlos} and Guti{\'e}rrez, {Rodrigo A.} and Jochen Hampe and {De Ferrari}, {Giancarlo V.} and Miquel, {Juan Francisco}",
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Bustos, BI, Pérez-Palma, E, Buch, S, Azócar, L, Riveras, E, Ugarte, GD, Toliat, M, Nürnberg, P, Lieb, W, Franke, A, Hinz, S, Burmeister, G, von Schönfels, W, Schafmayer, C, Völzke, H, Völker, U, Homuth, G, Lerch, MM, Santos, JL, Puschel, K, Bambs, C, Roa, JC, Gutiérrez, RA, Hampe, J, De Ferrari, GV & Miquel, JF 2019, 'Variants in ABCG8 and TRAF3 genes confer risk for gallstone disease in admixed Latinos with Mapuche Native American ancestry', Scientific Reports, vol. 9, n.º 1, 772. https://doi.org/10.1038/s41598-018-35852-z

Variants in ABCG8 and TRAF3 genes confer risk for gallstone disease in admixed Latinos with Mapuche Native American ancestry. / Bustos, Bernabé I.; Pérez-Palma, Eduardo; Buch, Stephan; Azócar, Lorena; Riveras, Eleodoro; Ugarte, Giorgia D.; Toliat, Mohammad; Nürnberg, Peter; Lieb, Wolfgang; Franke, Andre; Hinz, Sebastian; Burmeister, Greta; von Schönfels, Witigo; Schafmayer, Clemens; Völzke, Henry; Völker, Uwe; Homuth, Georg; Lerch, Markus M.; Santos, José Luis; Puschel, Klaus; Bambs, Claudia; Roa, Juan Carlos; Gutiérrez, Rodrigo A.; Hampe, Jochen; De Ferrari, Giancarlo V.; Miquel, Juan Francisco.

En: Scientific Reports, Vol. 9, N.º 1, 772, 28.01.2019.

Resultado de la investigación: Article

TY - JOUR

T1 - Variants in ABCG8 and TRAF3 genes confer risk for gallstone disease in admixed Latinos with Mapuche Native American ancestry

AU - Bustos, Bernabé I.

AU - Pérez-Palma, Eduardo

AU - Buch, Stephan

AU - Azócar, Lorena

AU - Riveras, Eleodoro

AU - Ugarte, Giorgia D.

AU - Toliat, Mohammad

AU - Nürnberg, Peter

AU - Lieb, Wolfgang

AU - Franke, Andre

AU - Hinz, Sebastian

AU - Burmeister, Greta

AU - von Schönfels, Witigo

AU - Schafmayer, Clemens

AU - Völzke, Henry

AU - Völker, Uwe

AU - Homuth, Georg

AU - Lerch, Markus M.

AU - Santos, José Luis

AU - Puschel, Klaus

AU - Bambs, Claudia

AU - Roa, Juan Carlos

AU - Gutiérrez, Rodrigo A.

AU - Hampe, Jochen

AU - De Ferrari, Giancarlo V.

AU - Miquel, Juan Francisco

PY - 2019/1/28

Y1 - 2019/1/28

N2 - Latin Americans and Chilean Amerindians have the highest prevalence of gallstone disease (GSD) and gallbladder cancer (GBC) in the world. A handful of loci have been associated with GSD in populations of predominantly European ancestry, however, they only explain a small portion of the genetic component of the disease. Here, we performed a genome-wide association study (GWAS) for GSD in 1,095 admixed Chilean Latinos with Mapuche Native American ancestry. Disease status was assessed by cholecystectomy or abdominal ultrasonography. Top-10 candidate variants surpassing the suggestive cutoff of P < 1 × 10 −5 in the discovery cohort were genotyped in an independent replication sample composed of 1,643 individuals. Variants with positive replication were further examined in two European GSD populations and a Chilean GBC cohort. We consistently replicated the association of ABCG8 gene with GSD (rs11887534, P = 3.24 × 10 −8 , OR = 1.74) and identified TRAF3 (rs12882491, P = 1.11 × 10 −7 , OR = 1.40) as a novel candidate gene for the disease in admixed Chilean Latinos. ABCG8 and TRAF3 variants also conferred risk to GBC. Gene expression analyses indicated that TRAF3 was significantly decreased in gallbladder (P = 0.015) and duodenal mucosa (P = 0.001) of GSD individuals compared to healthy controls, where according to GTEx data in the small intestine, the presence of the risk allele contributes to the observed effect. We conclude that ABCG8 and TRAF3 genes are associated with GSD and GBC in admixed Latinos and that decreased TRAF3 levels could enhance gallbladder inflammation as is observed in GSD and GSD-associated GBC.

AB - Latin Americans and Chilean Amerindians have the highest prevalence of gallstone disease (GSD) and gallbladder cancer (GBC) in the world. A handful of loci have been associated with GSD in populations of predominantly European ancestry, however, they only explain a small portion of the genetic component of the disease. Here, we performed a genome-wide association study (GWAS) for GSD in 1,095 admixed Chilean Latinos with Mapuche Native American ancestry. Disease status was assessed by cholecystectomy or abdominal ultrasonography. Top-10 candidate variants surpassing the suggestive cutoff of P < 1 × 10 −5 in the discovery cohort were genotyped in an independent replication sample composed of 1,643 individuals. Variants with positive replication were further examined in two European GSD populations and a Chilean GBC cohort. We consistently replicated the association of ABCG8 gene with GSD (rs11887534, P = 3.24 × 10 −8 , OR = 1.74) and identified TRAF3 (rs12882491, P = 1.11 × 10 −7 , OR = 1.40) as a novel candidate gene for the disease in admixed Chilean Latinos. ABCG8 and TRAF3 variants also conferred risk to GBC. Gene expression analyses indicated that TRAF3 was significantly decreased in gallbladder (P = 0.015) and duodenal mucosa (P = 0.001) of GSD individuals compared to healthy controls, where according to GTEx data in the small intestine, the presence of the risk allele contributes to the observed effect. We conclude that ABCG8 and TRAF3 genes are associated with GSD and GBC in admixed Latinos and that decreased TRAF3 levels could enhance gallbladder inflammation as is observed in GSD and GSD-associated GBC.

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DO - 10.1038/s41598-018-35852-z

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