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Gallstones, body mass index, C-reactive protein and gallbladder cancer—Mendelian randomization analysis of chilean and European genotype data.
Hepatology 73, 1783-1796 (2021)
Verlagsversion
Postprint
DOI
PMC
BACKGROUND & AIMS: Gallbladder cancer (GBC) is a neglected disease with substantial geographical variability: Chile shows the highest incidence worldwide, while GBC is relatively rare in Europe. Here we investigate the causal effects of risk factors considered in current GBC prevention programmes as well as C-reactive protein (CRP) level as a marker of chronic inflammation. APPROACH & RESULTS: We applied two-sample Mendelian randomization (MR) using publicly available data and our own data from a retrospective Chilean and a prospective European study. Causality was assessed by inverse variance weighted (IVW), MR-Egger regression and weighted median estimates complemented with sensitivity analyses on potential heterogeneity and pleiotropy, two-step MR and mediation analysis. We found evidence for a causal effect of gallstone disease on GBC risk in Chileans (p = 9 × 10-5 ) and Europeans (p = 9 × 10-5 ). A genetically elevated body mass index (BMI) increased GBC risk in Chileans (p = 0.03), while higher CRP concentrations increased GBC risk in Europeans (p = 4.1 × 10-6 ). European results suggest causal effects of BMI on gallstone disease (p = 0.008); public Chilean data were not, however, available to enable assessment of the mediation effects among causal GBC risk factors. CONCLUSIONS: Two risk factors considered in the current Chilean programme for GBC prevention are causally linked to GBC risk: gallstones and BMI. For Europeans, BMI showed a causal effect on gallstone risk, which was itself causally linked to GBC risk.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Times Cited
Scopus
Cited By
Cited By
Altmetric
17.425
2.762
1
7
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
C-reactive Protein ; Gallbladder Cancer ; Gallstones ; Mendelian Randomization ; Native American Ancestry; Reproductive Factors; Genetic-variants; Risk-factors; Life-style; Disease; Association; Adiposity; Weight; Susceptibility; Inflammation
Sprache
englisch
Veröffentlichungsjahr
2021
Prepublished im Jahr
2020
HGF-Berichtsjahr
2020
ISSN (print) / ISBN
0270-9139
e-ISSN
1527-3350
Zeitschrift
Hepatology
Quellenangaben
Band: 73,
Heft: 5,
Seiten: 1783-1796
Verlag
Wiley
Verlagsort
Hoboken, NJ
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Epidemiology (EPI)
POF Topic(s)
30202 - Environmental Health
Forschungsfeld(er)
Genetics and Epidemiology
PSP-Element(e)
G-504091-001
Förderungen
Heidelberg University
Deutsche Forschungsgemeinschaft Universitaet Heidelberg - Programme Open Access Publishing
Bundesministerium für Bildung und Forschung
UK Biobank Resource
Biobanking and Biomolecular Research Infrastructure - Large Prospective Cohorts
H2020 European Research CouncilH2020 European Research Council
Deutsche Forschungsgemeinschaft Universitaet Heidelberg - Programme Open Access Publishing
Bundesministerium für Bildung und Forschung
UK Biobank Resource
Biobanking and Biomolecular Research Infrastructure - Large Prospective Cohorts
H2020 European Research CouncilH2020 European Research Council
WOS ID
WOS:000645289400012
Scopus ID
85104970954
PubMed ID
32893372
Erfassungsdatum
2021-02-08