Genome-wide association analysis on five isolated populations identifies variants of the HLA-DOA gene associated with white wine liking

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:C4T 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. INTRODUCTIONWine is probably the oldest produced beverage in human history dating its first apparition in Georgia 7000 BC. It is extremely important for many cultures not only for its economy but also from the social and religious point of view. For these reasons it is also the most common and consumed type of alcoholic beverage throughout the world. 1,2 In addition, several studies indicate that modest wine consumption can have some beneficial health effects, including protection against cardiovascular and Alzheimer's disease. [3][4][5][6] There has been extensive research aiming to improve both its production and its flavor. The taste of wine depends on many different sensory perceptions ranging from taste and olfaction to texture. 7 Wine is a mixture of thousands of molecules that can contribute to its final taste, 8 and its composition varies greatly depending on the grapes used, climate and production method. 9 Although the flavor of some of these compounds is very well known, it is really difficult to understand what their role in final taste is. 7,10,11 The relevant role of genetic factors both on alcohol consumption and dependence has been clearly demonstrated by genome-wide association study (GWAS) studies. [12][13][14][15][16] Moreover, studies on the genetic variations in bitter taste receptors have also shown that variations in TAS2R16 and TAS2R38 genes can influence alcohol intake [17][18][19] but not dependence. 19 On the contrary, very little is known about the possible contribution of genetic factors to alcohol preferences in humans. Recen...

What has GWAS done for HLA and disease associations?

“…GWAS have shown associations of xMHC variants not only with autoimmune disorders and infectious diseases (Chapman & Hill, ; Handunnetthi et al., ; Rioux et al., ) as expected, but also with a diverse set of other diseases such as Barrett oesophagus (Su et al., ), metabolic disorders (Chasman et al., ), obesity (Thorleifsson et al., ), schizophrenia (S. W. G. o. t. P. G. Consortium, ; Ripke et al., ; Sekar et al., ), Parkinson disease (Nalls et al., ), age‐related macular degeneration (Cipriani et al., ), drug hypersensitivities (Profaizer & Eckels, ) and even with educational attainment (Rietveld et al., ) and wine preference (Pirastu et al., ). The potential reasons for such a large number of xMHC associations with a variety of traits are listed in Box 2.…”

“…GWAS have shown associations of xMHC variants not only with autoimmune disorders and infectious diseases(Chapman & Hill, 2012;Handunnetthi et al, 2010;Rioux et al, 2009) as expected, but also with a diverse set of other diseases such as Barrett oesophagus(Su et al, 2012), metabolic disorders(Chasman et al, 2009), obesity(Thorleifsson et al, 2009), schizophrenia (S. W. G. o. t. P. G Consortium, 2014;Ripke et al, 2013;Sekar et al, 2016),. Parkinson disease(Nalls et al, 2011), age-related macular degeneration(Cipriani et al, 2012), drug hypersensitivities(Profaizer & Eckels, 2012) and even with educational attainment(Rietveld et al, 2013) and wine preference(Pirastu et al, 2015). The potential reasons for such a large number of xMHC associations with a variety of traits are listed in Box 2.Another point relevant to any discussion of the xMHC in the pathogenesis of any disease and to possible explanation of extraordinarily large numbers of disease associations with its variants is the trans-eQTL effects of xMHC SNPs(Fairfax et al, 2012;Fehrmann et al, 2011;Westra et al, 2013).…”

A Brief Review of Genetic Approaches to the Study of Food Preferences: Current Knowledge and Future Directions

“…However, over the last few decades, rapid advances in molecular genetics have revolutionized the understanding of individual differences in many aspects of human behavior. These advances give researchers the tools to conduct genetic association studies on a large scale to better understand the role of specific gene loci in sensory perceptions, food liking/disliking, preference, and intake, as well as on food-related habits [13,14,15,16,17,18].…”

“…The effects of taste and smell genes on food habits [19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36] and health status [30,31,37,38,39,40,41,42,43,44,45,46,47,48] have also been extensively investigated. However, gaps in understanding still exist, and emerging evidence suggests that novel genes (not necessarily related to taste or smell perception) may play a critical role in these relationships [13,14,15,16].…”

Influence of yeasts of the genus Saccharomyces and not Saccharomyces in elaboration of white wines

“…Wine is extremely important to many people, from an economic point of view, but also by social, cultural, gastronomic and religious aspects. In addition, the literature indicates that wine consumption may promote some beneficial health effects, including protection against cardiovascular disease and Alzheimer's disease [2].…”