Copy number variants in lipid metabolism genes are associated with gallstones disease in men

Eduardo Pérez-Palma, Bernabé I. Bustos, Dennis Lal, Stephan Buch, Lorena Azocar, Mohammad Reza Toliat, Wolfgang Lieb, Andre Franke, Sebastian Hinz, Greta Burmeister, Witigo von Shönfels, Clemens Schafmayer, Peter Ahnert, Henry Völzke, Uwe Völker, Georg Homuth, Markus M. Lerch, Klaus Puschel, Rodrigo A. Gutiérrez, Jochen HampePeter Nürnberg, Juan Francisco Miquel, Giancarlo V. De Ferrari

Resultado de la investigación: Article

Resumen

Gallstones Disease (GSD) is one of the most common digestive diseases requiring hospitalization and surgical procedures in the world. GSD has a high prevalence in populations with European or Amerindian ancestry (10–20%) and the influence of genetic factors is broadly acknowledged. However, known genetic variants do not entirely explain the disease heritability suggesting that additional genetic variants remain to be identified. Here, we examined the association of copy number variants (CNVs) with GSD in a sample of 4778 individuals (1929 GSD cases and 2849 controls) including two European cohorts from Germany (n = 3702) and one admixed Latin American cohort from Chile (n = 1076). We detected 2936 large and rare CNVs events (size > 100 kb, frequency < 1%). Case-control burden analysis and generalized linear regression models revealed significant association of CNVs with GSD in men, with the strongest effect observed with CNVs overlapping lipid metabolism genes (p-value = 6.54 × 10–4; OR = 2.76; CI 95% = 1.53–4.89). Our results indicate a clear link between CNVs and GSD in men and provides additional evidence that the genetic components of risk for GSD are complex, can be sex specific and include CNVs affecting genes involved in lipid metabolism.

Idioma originalEnglish
PublicaciónEuropean Journal of Human Genetics
DOI
EstadoAccepted/In press - 1 ene 2019

Huella dactilar

Gallstones
Lipid Metabolism
Genes
Linear Models
Chile
Germany
Hospitalization

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Citar esto

Pérez-Palma, Eduardo ; Bustos, Bernabé I. ; Lal, Dennis ; Buch, Stephan ; Azocar, Lorena ; Toliat, Mohammad Reza ; Lieb, Wolfgang ; Franke, Andre ; Hinz, Sebastian ; Burmeister, Greta ; von Shönfels, Witigo ; Schafmayer, Clemens ; Ahnert, Peter ; Völzke, Henry ; Völker, Uwe ; Homuth, Georg ; Lerch, Markus M. ; Puschel, Klaus ; Gutiérrez, Rodrigo A. ; Hampe, Jochen ; Nürnberg, Peter ; Francisco Miquel, Juan ; De Ferrari, Giancarlo V. / Copy number variants in lipid metabolism genes are associated with gallstones disease in men. En: European Journal of Human Genetics. 2019.
@article{76c43ce117ed4ec1a93bfe0ad429bff0,
title = "Copy number variants in lipid metabolism genes are associated with gallstones disease in men",
abstract = "Gallstones Disease (GSD) is one of the most common digestive diseases requiring hospitalization and surgical procedures in the world. GSD has a high prevalence in populations with European or Amerindian ancestry (10–20{\%}) and the influence of genetic factors is broadly acknowledged. However, known genetic variants do not entirely explain the disease heritability suggesting that additional genetic variants remain to be identified. Here, we examined the association of copy number variants (CNVs) with GSD in a sample of 4778 individuals (1929 GSD cases and 2849 controls) including two European cohorts from Germany (n = 3702) and one admixed Latin American cohort from Chile (n = 1076). We detected 2936 large and rare CNVs events (size > 100 kb, frequency < 1{\%}). Case-control burden analysis and generalized linear regression models revealed significant association of CNVs with GSD in men, with the strongest effect observed with CNVs overlapping lipid metabolism genes (p-value = 6.54 × 10–4; OR = 2.76; CI 95{\%} = 1.53–4.89). Our results indicate a clear link between CNVs and GSD in men and provides additional evidence that the genetic components of risk for GSD are complex, can be sex specific and include CNVs affecting genes involved in lipid metabolism.",
author = "Eduardo P{\'e}rez-Palma and Bustos, {Bernab{\'e} I.} and Dennis Lal and Stephan Buch and Lorena Azocar and Toliat, {Mohammad Reza} and Wolfgang Lieb and Andre Franke and Sebastian Hinz and Greta Burmeister and {von Sh{\"o}nfels}, Witigo and Clemens Schafmayer and Peter Ahnert and Henry V{\"o}lzke and Uwe V{\"o}lker and Georg Homuth and Lerch, {Markus M.} and Klaus Puschel and Guti{\'e}rrez, {Rodrigo A.} and Jochen Hampe and Peter N{\"u}rnberg and {Francisco Miquel}, Juan and {De Ferrari}, {Giancarlo V.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1038/s41431-019-0501-7",
language = "English",
journal = "European Journal of Human Genetics",
issn = "1018-4813",
publisher = "Nature Publishing Group",

}

Pérez-Palma, E, Bustos, BI, Lal, D, Buch, S, Azocar, L, Toliat, MR, Lieb, W, Franke, A, Hinz, S, Burmeister, G, von Shönfels, W, Schafmayer, C, Ahnert, P, Völzke, H, Völker, U, Homuth, G, Lerch, MM, Puschel, K, Gutiérrez, RA, Hampe, J, Nürnberg, P, Francisco Miquel, J & De Ferrari, GV 2019, 'Copy number variants in lipid metabolism genes are associated with gallstones disease in men', European Journal of Human Genetics. https://doi.org/10.1038/s41431-019-0501-7

Copy number variants in lipid metabolism genes are associated with gallstones disease in men. / Pérez-Palma, Eduardo; Bustos, Bernabé I.; Lal, Dennis; Buch, Stephan; Azocar, Lorena; Toliat, Mohammad Reza; Lieb, Wolfgang; Franke, Andre; Hinz, Sebastian; Burmeister, Greta; von Shönfels, Witigo; Schafmayer, Clemens; Ahnert, Peter; Völzke, Henry; Völker, Uwe; Homuth, Georg; Lerch, Markus M.; Puschel, Klaus; Gutiérrez, Rodrigo A.; Hampe, Jochen; Nürnberg, Peter; Francisco Miquel, Juan; De Ferrari, Giancarlo V.

En: European Journal of Human Genetics, 01.01.2019.

Resultado de la investigación: Article

TY - JOUR

T1 - Copy number variants in lipid metabolism genes are associated with gallstones disease in men

AU - Pérez-Palma, Eduardo

AU - Bustos, Bernabé I.

AU - Lal, Dennis

AU - Buch, Stephan

AU - Azocar, Lorena

AU - Toliat, Mohammad Reza

AU - Lieb, Wolfgang

AU - Franke, Andre

AU - Hinz, Sebastian

AU - Burmeister, Greta

AU - von Shönfels, Witigo

AU - Schafmayer, Clemens

AU - Ahnert, Peter

AU - Völzke, Henry

AU - Völker, Uwe

AU - Homuth, Georg

AU - Lerch, Markus M.

AU - Puschel, Klaus

AU - Gutiérrez, Rodrigo A.

AU - Hampe, Jochen

AU - Nürnberg, Peter

AU - Francisco Miquel, Juan

AU - De Ferrari, Giancarlo V.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Gallstones Disease (GSD) is one of the most common digestive diseases requiring hospitalization and surgical procedures in the world. GSD has a high prevalence in populations with European or Amerindian ancestry (10–20%) and the influence of genetic factors is broadly acknowledged. However, known genetic variants do not entirely explain the disease heritability suggesting that additional genetic variants remain to be identified. Here, we examined the association of copy number variants (CNVs) with GSD in a sample of 4778 individuals (1929 GSD cases and 2849 controls) including two European cohorts from Germany (n = 3702) and one admixed Latin American cohort from Chile (n = 1076). We detected 2936 large and rare CNVs events (size > 100 kb, frequency < 1%). Case-control burden analysis and generalized linear regression models revealed significant association of CNVs with GSD in men, with the strongest effect observed with CNVs overlapping lipid metabolism genes (p-value = 6.54 × 10–4; OR = 2.76; CI 95% = 1.53–4.89). Our results indicate a clear link between CNVs and GSD in men and provides additional evidence that the genetic components of risk for GSD are complex, can be sex specific and include CNVs affecting genes involved in lipid metabolism.

AB - Gallstones Disease (GSD) is one of the most common digestive diseases requiring hospitalization and surgical procedures in the world. GSD has a high prevalence in populations with European or Amerindian ancestry (10–20%) and the influence of genetic factors is broadly acknowledged. However, known genetic variants do not entirely explain the disease heritability suggesting that additional genetic variants remain to be identified. Here, we examined the association of copy number variants (CNVs) with GSD in a sample of 4778 individuals (1929 GSD cases and 2849 controls) including two European cohorts from Germany (n = 3702) and one admixed Latin American cohort from Chile (n = 1076). We detected 2936 large and rare CNVs events (size > 100 kb, frequency < 1%). Case-control burden analysis and generalized linear regression models revealed significant association of CNVs with GSD in men, with the strongest effect observed with CNVs overlapping lipid metabolism genes (p-value = 6.54 × 10–4; OR = 2.76; CI 95% = 1.53–4.89). Our results indicate a clear link between CNVs and GSD in men and provides additional evidence that the genetic components of risk for GSD are complex, can be sex specific and include CNVs affecting genes involved in lipid metabolism.

UR - http://www.scopus.com/inward/record.url?scp=85072170546&partnerID=8YFLogxK

U2 - 10.1038/s41431-019-0501-7

DO - 10.1038/s41431-019-0501-7

M3 - Article

C2 - 31485028

AN - SCOPUS:85072170546

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

SN - 1018-4813

ER -