title: Non-additive genome-wide association scan reveals a new gene associated with habitual coffee consumption.
abstract: Coffee is one of the most consumed beverages world-wide and one of the primary sources of caffeine intake. Given its important health and economic impact, the underlying genetics of its consumption has been widely studied. Despite these efforts, much has still to be uncovered. In particular, the use of non-additive genetic models may uncover new information about the genetic variants driving coffee consumption. We have conducted a genome-wide association study in two Italian populations using additive, recessive and dominant models for analysis. This has uncovered a significant association in the PDSS2 gene under the recessive model that has been replicated in an independent cohort from the Netherlands (ERF). The identified gene has been shown to negatively regulate the expression of the caffeine metabolism genes and can thus be linked to coffee consumption. Further bioinformatics analysis of eQTL and histone marks from Roadmap data has evidenced a possible role of the identified SNPs in regulating PDSS2 gene expression through enhancers present in its intron. Our results highlight a novel gene which regulates coffee consumption by regulating the expression of the genes linked to caffeine metabolism. Further studies will be needed to clarify the biological mechanism which links PDSS2 and coffee consumption.
authors: Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste Italy.|University of Trieste, Trieste, Italy.|Usher Institute of Population Health and Informatics, The University of Edinburgh, Edinburgh, UK.
authors: Nicola
authors: N
authors: Pirastu
authors: Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors: Maarten
authors: M
authors: Kooyman
authors: Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste Italy.
authors: Antonietta
authors: A
authors: Robino
authors: Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors: Ashley
authors: A
authors: van der Spek
authors: illycaffe's.p.a, Trieste, Italy.
authors: Luciano
authors: L
authors: Navarini
authors: Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors: Najaf
authors: N
authors: Amin
authors: Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.|PolyOmica, Groningen, The Netherlands.
authors: Lennart C
authors: LC
authors: Karssen
authors: Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.|Centre for Medical Systems Biology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Cornelia M
authors: CM
authors: Van Duijn
authors: Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste Italy.|University of Trieste, Trieste, Italy.
authors: Paolo
authors: P
authors: Gasparini
mesh_terms: D000328:Adult; D019883:Alkyl and Aryl Transferases / Q000235:genetics* / Q000378:metabolism; D002110:Caffeine / Q000008:administration & dosage* / Q000378:metabolism; D003069:Coffee; D015331:Cohort Studies; D004327:Drinking Behavior; D005260:Female; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D003069:Coffee; D002110:Caffeine; D019883:Alkyl and Aryl Transferases; C540142:prenyl diphosphate synthase, subunit 2, human