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.
N1 - Funding Information:
Acknowledgements We thank the patients and relatives who participated in this study. We thank the German Ministry of Education and Research funding through the POPGEN Biobank project (01GS0426, 01GR0468). We thank the Community Medicine Research Net of the University of Greifswald, the Ministry of Cultural Affairs, and the Social Ministry of the Federal State of Mecklenburg-West Pomerania for access to the Study of Health in Pomerania, SHIP project (01ZZ9603, 01ZZ0103, and 01ZZ0701). We thank the FONDAP Center for Genome Regulation Project (CGR; 1509000) and the Chilean National Fund for Development in Science and Technology (FONDECYT) project numbers: 1130303 (JFM) and 1140353, 1180848 (GVD). We thank the Chilean National Commission for Scientific and Technological Research (CONICYT) and the German Academic Exchange Service (DAAD) for support to E. Pérez-Palma and B.I. Bustos.
Publisher Copyright:
© 2019, The Author(s).
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
SN - 1018-4813
VL - 28
SP - 264
EP - 273
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 2
ER -