Abstract
Wine is the most popular alcoholic beverage around the world and because of its importance in society has been widely studied. Understanding what drives its flavor has been a quest for decades but much is still unknown and will be determined at least in part by individual taste preferences. Recently studies in the genetics of taste have uncovered the role of different genes in the determination of food preferences giving new insight on its physiology. In this context we have performed a genome-wide association study on red and white wine liking using three isolated populations collected in Italy, and replicated our results on two additional populations coming from the Netherland and Central Asia for a total of 3885 samples. We have found a significant association (P=2.1 × 10−8) between white wine liking and rs9276975:C>T a polymorphism in the HLA-DOA gene encoding a non-canonical MHC II molecule, which regulates other MHC II molecules. The same association was also found with red wine liking (P=8.3 × 10−6). Sex-separated analysis have also revealed that the effect of HLA-DOA is twice as large in women as compared to men suggesting an interaction between this polymorphism and gender. Our results are one of the first examples of genome-wide association between liking of a commonly consumed food and gene variants. Moreover, our results suggest a role of the MHC system in the determination of food preferences opening new insight in this field in general.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Sieri S, Agudo A, Kesse E et al: Patterns of alcohol consumption in 10 European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) project. Public Health Nutr 2002; 5: 1287–1296.
Schröder H, Ferrández O, Jimenez Conde J, Sánchez-Font A, Marrugat J : Cardiovascular risk profile and type of alcohol beverage consumption: a population-based study. Ann Nutr Metab 49: 100–106.
Rimm EB, Giovannucci EL, Willett WC et al: Prospective study of alcohol consumption and risk of coronary disease in men. Lancet 1991; 338: 464–468.
Marmot MG : Alcohol and coronary heart disease. Int J Epidemiol 2001; 30: 724–729.
Di Castelnuovo A, Rotondo S, Iacoviello L, Donati MB, De Gaetano G : Meta-analysis of wine and beer consumption in relation to vascular risk. Circulation 2002; 105: 2836–2844.
Tolstrup J, Jensen MK, Tjønneland A, Overvad K, Mukamal KJ, Grønbaek M : Prospective study of alcohol drinking patterns and coronary heart disease in women and men. BMJ 2006; 332: 1244–1248.
Polásková P, Herszage J, Ebeler SE : Wine flavor: chemistry in a glass. Chem Soc Rev 2008; 37: 2478–2489.
Rapp A : Volatile flavour of wine: correlation between instrumental analysis and sensory perception. Nahrung 1998; 42: 351–363.
Moreno-Arribas MV, Polo MC : Winemaking biochemistry and microbiology: current knowledge and future trends. Crit Rev Food Sci Nutr 2005; 45: 265–286.
Ardö Y : Flavour formation by amino acid catabolism. Biotechnol Adv 24: 238–242.
Snowdon EM, Bowyer MC, Grbin PR, Bowyer PK : Mousy off-flavor: a review. J Agric Food Chem 2006; 54: 6465–6474.
Kapoor M, Wang J-C, Wetherill L et al: A meta-analysis of two genome-wide association studies to identify novel loci for maximum number of alcoholic drinks. Hum Genet 2013; 132: 1141–1151.
Bierut LJ, Agrawal A, Bucholz KK et al: A genome-wide association study of alcohol dependence. Proc Natl Acad Sci USA 2010; 107: 5082–5087.
Edenberg HJ, Koller DL, Xuei X et al: Genome-wide association study of alcohol dependence implicates a region on chromosome 11. Alcohol Clin Exp Res 2010; 34: 840–852.
Lind PA, Macgregor S, Vink JM et al: A genomewide association study of nicotine and alcohol dependence in Australian and Dutch populations. Twin Res Hum Genet 2010; 13: 10–29.
Frank J, Cichon S, Treutlein J et al: Genome-wide significant association between alcohol dependence and a variant in the ADH gene cluster. Addict Biol 2012; 17: 171–180.
Hayes JE, Wallace MR, Knopik VS, Herbstman DM, Bartoshuk LM, Duffy VB : Allelic variation in TAS2R bitter receptor genes associates with variation in sensations from and ingestive behaviors toward common bitter beverages in adults. Chem Senses 2011; 36: 311–319.
Duffy VB, Davidson AC, Kidd JR et al: Bitter receptor gene (TAS2R38), 6-n-propylthiouracil (PROP) bitterness and alcohol intake. Alcohol Clin Exp Res 2004; 28: 1629–1637.
Wang JC, Hinrichs AL, Bertelsen S et al: Functional variants in TAS2R38 and TAS2R16 influence alcohol consumption in high-risk families of African-American origin. Alcohol Clin Exp Res 2007; 31: 209–215.
Knaapila A, Hwang L-D, Lysenko A et al: Genetic analysis of chemosensory traits in human twins. Chem Senses 2012; 37: 869–881.
McRae JF, Mainland JD, Jaeger SR, Adipietro KA, Matsunami H, Newcomb RD : Genetic variation in the odorant receptor OR2J3 is associated with the ability to detect the ‘grassy’ smelling odor, cis-3-hexen-1-ol. Chem Senses 2012; 37: 585–593.
Pirastu N, Robino A, Lanzara C et al: Genetics of Food Preferences: A First View from Silk Road Populations. J Food Sci 2012; 77: S413–S418.
JONES LV, PERYAM DR, THURSTONE LL : Development of a scale for measuring soldiers’food preferences b. J Food Sci 1955; 20: 512–520.
Coetzee H, Taylor JRN : The use and adaptation of the paired-comparison method in the sensory evaluation of hamburger-type patties by illiterate/semi-literate consumers. Food Qual Prefer 1996; 7: 81–85.
Colman AM, Norris CE : PCC. Comparing Rating Scales of Different Lengths: Equivalence of Scores From 5-Point and 7-Point Scales. Psychol Rep 1997; 80: 355–362.
Preston CC, Colman AM : Optimal number of response categories in rating scales: reliability, validity, discriminating power, and respondent preferences. Acta Psychol (Amst) 2000; 104: 1–15.
J.G. D: Five point vs eleven point scales: does it make a difference to data characteristics? Australas J Mark Res 2002; 10: 39–47.
Girotto G, Pirastu N, Sorice R et al: Hearing function and thresholds: a genome-wide association study in European isolated populations identifies new loci and pathways. J Med Genet 2011; 48: 369–374.
Aulchenko YS, Heutink P, Mackay I et al: Linkage disequilibrium in young genetically isolated Dutch population. Eur J Hum Genet 2004; 12: 527–534.
Pardo LM, MacKay I, Oostra B, van Duijn CM, Aulchenko YS : The effect of genetic drift in a young genetically isolated population. Ann Hum Genet 2005; 69: 288–295.
Delaneau O, Zagury J-F, Marchini J : Improved whole-chromosome phasing for disease and population genetic studies. Nat Methods 2013; 10: 5–6.
Howie BN, Donnelly P, Marchini J : A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet 2009; 5: e1000529.
Abecasis GR, Auton A, Brooks LD et al: An integrated map of genetic variation from 1,092 human genomes. Nature 2012; 491: 56–65.
Howie B, Fuchsberger C, Stephens M, Marchini J, Abecasis GR : Fast and accurate genotype imputation in genome-wide association studies through pre-phasing. Nat Genet 2012; 44: 955–959.
Aulchenko YS, Ripke S, Isaacs A, van Duijn CM : GenABEL: an R library for genome-wide association analysis. Bioinformatics 2007; 23: 1294–1296.
Belonogova NM, Svishcheva GR, van Duijn CM, Aulchenko YS, Axenovich TI : Region-based association analysis of human quantitative traits in related individuals. PLoS One 2013; 8: e65395.
Hirschhorn JN, Daly MJ : Genome-wide association studies for common diseases and complex traits. Nat Rev Genet 2005; 6: 95–108.
Purcell S, Cherny SS, Sham PC : Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics 2003; 19: 149–150.
Ward LD, Kellis M : HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants. Nucleic Acids Res 2012; 40: D930–D934.
Schulze M-SED, Wucherpfennig KW : The mechanism of HLA-DM induced peptide exchange in the MHC class II antigen presentation pathway. Curr Opin Immunol 2012; 24: 105–111.
Wedekind C, Seebeck T, Bettens F, Paepke AJ : MHC-dependent mate preferences in humans. Proc Biol Sci 1995; 260: 245–249.
Ober C, Weitkamp LR, Cox N, Dytch H, Kostyu D, Elias S : HLA and mate choice in humans. Am J Hum Genet 1997; 61: 497–504.
Capittini C, Martinetti M, Cuccia M : MHC variation, mate choice and natural selection: the scent of evolution. Riv Biol 101: 463–480.
Ishii T, Mombaerts P : Expression of nonclassical class I major histocompatibility genes defines a tripartite organization of the mouse vomeronasal system. J Neurosci 2008; 28: 2332–2341.
Leinders-Zufall T, Ishii T, Mombaerts P, Zufall F, Boehm T : Structural requirements for the activation of vomeronasal sensory neurons by MHC peptides. Nat Neurosci 2009; 12: 1551–1558.
Wysocki CJ, Yamazaki K, Curran M, Wysocki LM, Beauchamp GK : Mice (Mus musculus) lacking a vomeronasal organ can discriminate MHC-determined odortypes. Horm Behav 2004; 46: 241–246.
Strandh M, Westerdahl H, Pontarp M et al: Major histocompatibility complex class II compatibility, but not class I, predicts mate choice in a bird with highly developed olfaction. Proc Biol Sci 2012; 279: 4457–4463.
Milinski M : Evidence for MHC-correlated perfume preferences in humans. Behav Ecol 2001; 12: 140–149.
Hämmerli A, Schweisgut C, Kaegi M : Population genetic segmentation of MHC-correlated perfume preferences. Int J Cosmet Sci 2012; 34: 161–168.
Singh PB, Herbert J, Roser B, Arnott L, Tucker DK, Brown RE : Rearing rats in a germ-free environment eliminates their odors of individuality. J Chem Ecol 1990; 16: 1667–1682.
Dinnella C, Recchia A, Tuorila H, Monteleone E : Individual astringency responsiveness affects the acceptance of phenol-rich foods. Appetite 2011; 56: 633–642.
Koelega HS, Köster EP : Some experiments on sex differences in odor perception. Ann N Y Acad Sci 1974; 237: 234–246.
Zucco GM, Aiello L, Turuani L, Köster E : Odor-evoked autobiographical memories: age and gender differences along the life span. Chem Senses 2012; 37: 179–189.
Santos PSC, Schinemann JA, Gabardo J, Bicalho M, da G : New evidence that the MHC influences odor perception in humans: a study with 58 Southern Brazilian students. Horm Behav 2005; 47: 384–388.
Wedekind C, Füri S : Body odour preferences in men and women: do they aim for specific MHC combinations or simply heterozygosity? Proc Biol Sci 1997; 264: 1471–1479.
Acknowledgements
We would like to thank all the participants in the study for their contribution and support. The SR study has been founded by the Region Friuli Venezia Giulia grant number 35\09 Linea 2 ‘Sulle tracce di Marco Polo: geni, gusto e loro implicazioni sulla salute lungo la Via della Seta’. The INGI-FVG study was founded through the Italian Ministry of health. We thank the inhabitants and the administrators of the Val Borbera for their participation in the study. A special thanks to Professor Clara Camaschella, Dr Silvia Bione, Dr Laura Crocco, Ms Maria Rosa Biglieri, Dr Diego Sabbi for help with the data collection. We thank Fondazione Compagnia di San Paolo, Torino, Fondazione Cariplo, Milano and Health Ministry (Progetto Finalizzato and Italian Centre for Disease Prevention and Control) for financial support. The ERF study as a part of EUROSPAN (European Special Populations Research Network) was supported by European Commission FP6 STRP grant number 018947 (LSHG-CT-2006-01947) and also received funding from the European Community's Seventh Framework Programme (FP7/2007-2013)/grant agreement HEALTH-F4-2007-201413 by the European Commission under the programme ‘Quality of Life and Management of the Living Resources’ of 5th Framework Programme (no. QLG2-CT-2002-01254). High-throughput analysis of the ERF data was supported by joint grant from the Netherlands Organisation for Scientific Research and the Russian Foundation for Basic Research (NWO-RFBR 047.017.043). We are grateful to all study participants and their relatives, general practitioners and neurologists for their contributions and to P Veraart for her help in genealogy, J Vergeer for the supervision of the laboratory work and P Snijders for his help in data collection. Statistical analyses were partly carried out on the Genetic Cluster Computer (http://www.geneticcluster.org), which is financially supported by the Netherlands Scientific Organization (NWO 480-05-003 PI: Posthuma) along with a supplement from the Dutch Brain Foundation and the VU University Amsterdam. This research was financially supported by BBMRI-NL, a Research Infrastructure financed by the Dutch Government (NWO 184.021.007).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Additional information
Supplementary Information accompanies this paper on European Journal of Human Genetics website
Supplementary information
Rights and permissions
About this article
Cite this article
Pirastu, N., Kooyman, M., Traglia, M. et al. Genome-wide association analysis on five isolated populations identifies variants of the HLA-DOA gene associated with white wine liking. Eur J Hum Genet 23, 1717–1722 (2015). https://doi.org/10.1038/ejhg.2015.34
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/ejhg.2015.34
