White Wine Liking

Introduction

Wine is a beverage with deep historical roots, first appearing around 7000 BC in Georgia, and holds significant cultural, economic, social, and religious importance across many societies. It is one of the most widely consumed alcoholic beverages globally.^[1]Beyond its cultural significance, moderate wine consumption has been associated with certain health benefits, including potential protection against cardiovascular disease and Alzheimer’s disease.^[1] The perception of wine flavor is a complex sensory experience, encompassing taste, olfaction, and texture, derived from a mixture of thousands of molecules whose roles in the final flavor profile are still being investigated.^[1]Understanding the factors that influence individual preferences for wine, such as white wine liking, is an active area of research.

Genetic Basis of Liking

Genetic factors are known to play a substantial role in various aspects of alcohol consumption and dependence.^[1] Research has identified genetic variations in bitter taste receptors, such as TAS2R16 and TAS2R38, that can influence alcohol intake, though not necessarily dependence.^[1] Beyond taste, the perception of ethanol flavor (distinct from taste) has been linked to variants in olfactory receptor genes like OR7D4 and genes encoding subunits of salt taste receptors, such as SCNN1D.^[1] Another olfactory receptor gene, OR2J3, has a non-synonymous variant that impairs the ability to detect cis-3-hexen-1-ol, a key component in many foods, including wine.^[1] Furthermore, variations in the TAS1R2 gene, a sweet receptor gene, have been associated with white wine and vodka liking in some Central Asian populations, suggesting a broader role in ethanol perception.^[1] Despite these findings, the precise molecular mechanisms underlying food liking, and specifically wine preference, remain largely unclear.^[1]A genome-wide association study (GWAS) has identified a significant association between white wine liking and a specific genetic variant,rs9276975 , located in the HLA-DOA gene.^[1] This polymorphism, situated in the 3′-untranslated region (3′-UTR) of the gene, suggests a potential regulatory role for HLA-DOA.^[1] HLA-DOA encodes a non-canonical MHC class II molecule involved in regulating other MHC class II molecules, specifically by inhibiting HLA-DM, which in turn prevents the general activation of MHC class II molecules.^[1] This association signal appears to be confined to the HLA-DOA locus, isolated from the wider HLA region by recombination hotspots.^[1] It is hypothesized that HLA-DOA, through its regulation of MHC class II molecules, might modulate the perception of specific volatile compounds in wine, possibly those produced by bacteria during wine production.^[1] This olfactory hypothesis is further supported by the observation that the effect of rs9276975 on wine liking is twice as strong in women compared to men, given that women are generally more sensitive to certain odors.^[1] The association with HLA-DOA appears to be specific to wine liking and not a general effect on other food preferences.^[1]

Understanding the genetic underpinnings of white wine liking has implications for both clinical and social contexts. From a clinical perspective, identifying genetic factors that influence food preferences can contribute to a deeper understanding of dietary choices and potentially inform personalized health recommendations. While the current research focuses on liking rather than consumption or health outcomes directly, it provides a foundation for exploring how genetic predispositions to specific food preferences might interact with broader health behaviors.

Socially, wine plays a significant role in human interaction and cultural practices. Delving into the genetics of wine liking can shed light on the diverse individual preferences observed within populations. This knowledge could also have implications for the wine industry, guiding efforts to improve production methods and tailor flavors to consumer preferences. Ultimately, discovering the genetic links between flavor and olfaction, as suggested by the role of MHC molecules in white wine liking, opens new avenues for research into human sensory perception and its impact on food choice.^[1]

Methodological and Statistical Considerations

The study’s power to detect genetic associations for white wine liking presents a notable limitation. While the meta-analysis included a total of 3885 samples from diverse populations, the reported power was 0.54 to detect associations at genome-wide significance (α = 5 × 10−8) for an effect size of β = 0.053 and a minor allele frequency (MAF) of 0.15, and 0.8 power for 0.01 explained variance.^[1]This suggests that the study may be underpowered to identify variants with smaller effect sizes or lower MAFs, potentially leading to an incomplete understanding of the trait’s genetic architecture. Consequently, other genetic loci contributing to white wine liking might remain undetected, necessitating larger cohorts or studies specifically designed to capture subtle genetic influences.

Phenotype ascertainment and replication across diverse populations also introduce complexities. White wine liking was assessed using self-reported questionnaires, which employed different rating scales: a 1-9 point scale for European populations and a 5-point scale with smiley faces for the Silk Road cohort, used to overcome potential linguistic barriers.^[1] Although data were standardized to make measures comparable, the inherent differences in scale design and the cultural context of “liking” could introduce subtle biases or variations in interpretation across cohorts. Furthermore, a previously reported association with a variant in the TAS1R2 gene in Central Asian populations did not replicate in the combined meta-analysis (P-value = 0.83), highlighting the challenges in replicating findings across genetically and culturally distinct groups and suggesting potential allelic heterogeneity.^[1]

Generalizability and Ancestry-Specific Effects

The study’s focus on five isolated populations from Europe and Central Asia, while beneficial for reducing genetic heterogeneity, inherently limits the direct generalizability of the findings to broader, outbred populations. Isolated populations often exhibit unique genetic structures and allele frequencies, meaning that genetic associations identified within these groups may not translate uniformly to more diverse populations with different genetic backgrounds and environmental exposures. The observed lack of replication for a TAS1R2 variant, attributed to “allelic heterogeneity between the SR populations and the European ones,” further underscores the potential for population-specific genetic effects, which could restrict the broader applicability of the current findings.^[1] Another significant consideration is the identification of sex-specific effects, where the association between rs9276975 and white wine liking was considerably stronger in women (P = 1 × 10−7) than in men (P = 0.01), with women displaying twice the effect size.^[1]While this differential effect was analyzed within the study, it highlights that genetic influences on complex traits like food liking can vary substantially between sexes. This necessitates that future genetic studies on white wine liking, and similar sensory traits, adequately account for sex as a biological variable to avoid underestimating or misinterpreting genetic contributions, and to ensure that findings are generalizable across both men and women.

Unexplored Factors and Mechanistic Gaps

White wine liking is a multifaceted phenotype influenced by numerous factors beyond genetics, including cultural background, environmental exposure, dietary habits, and socioeconomic status, which were not exhaustively accounted for as primary confounders in the study design.^[1]Although age and sex were included as covariates, unmeasured environmental factors could interact significantly with genetic predispositions, potentially modulating or even obscuring the true genetic effects. The complex interplay between genetic variants and environmental exposures, often termed gene-environment interaction, remains largely unexplored for white wine liking, contributing to the broader challenge of fully understanding the etiology of complex human traits.

Despite identifying a genome-wide significant association with rs9276975 in the 3′-UTR region of the HLA-DOAgene, the precise biological mechanism by which this variant influences white wine liking remains largely unknown. Bioinformatic analyses did not provide clear insights into a specific regulatory role forrs9276975 or SNPs in strong linkage disequilibrium, and the exact pathway linking HLA-DOA to olfactory perception or neural signaling related to liking requires further elucidation.^[1]This substantial mechanistic gap, coupled with the inherent complexity of sensory perception, implies that a considerable portion of the heritability of white wine liking likely remains unexplained by current genetic findings, underscoring the need for further functional studies and comprehensive genomic investigations.

Variants

The perception and enjoyment of white wine are complex traits influenced by a variety of genetic factors, including variants within genes associated with immune function and cellular structures. Among these, the HLA-DOAgene and its associated single nucleotide polymorphism (SNP)rs9276975 have been identified as having a significant role in individual white wine liking.HLA-DOA encodes a non-canonical Major Histocompatibility Complex (MHC) class II molecule, which plays a critical role in regulating other MHC class II molecules that are fundamental to the immune system’s ability to recognize antigens.^[1] The rs9276975 variant, located in the 3’-untranslated region (3’-UTR) of the HLA-DOAgene, is strongly associated with white wine liking, suggesting a regulatory rather than a direct functional impact on the protein itself.^[1] The mechanism by which HLA-DOAinfluences white wine liking is thought to involve its regulatory effect on MHC class II molecules, which in turn may modulate the perception of specific volatile compounds found in wine.HLA-DOA is known to inhibit HLA-DM, another non-canonical MHC class II molecule responsible for activating other MHC class II proteins and determining their antigen-binding specificity.^[1] This regulatory interplay could impact how the olfactory epithelium interacts with wine aromas, consequently shaping an individual’s preference. Notably, the association between rs9276975 and white wine liking is significantly stronger in women than in men, with women exhibiting twice the effect size, a finding that supports an olfactory hypothesis given women’s documented higher sensitivity to certain odors.^[1] Beyond immune-related genes, other genetic factors contribute to the intricate sensory experience of wine. The gene CFAP61 (Cilia And Flagella Associated Protein 61) is crucial for the proper assembly and function of cilia and flagella, which are cellular structures vital for various sensory processes. Specifically, olfactory cilia in the nasal cavity are instrumental in detecting and transducing odor signals, making CFAP61 a plausible candidate for influencing olfactory perception and, by extension, wine liking. A variant such as rs35829183 within CFAP61 could potentially alter the efficiency or sensitivity of these ciliary structures, thereby modifying an individual’s ability to perceive the subtle volatile compounds that define white wine flavor. The complex interplay of genes like CFAP61 and HLA-DOA underscores the multifaceted biological underpinnings of individual differences in taste and smell perception, highlighting how genetic variation can shape preferences for common foods and beverages.^[1] Understanding the genetic basis of such sensory preferences, including the role of olfactory mechanisms, is a growing field of research.^[1]

Key Variants

RS ID	Gene	Related Traits
rs9276975	HLA-DOA	red wine liking white wine liking
rs35829183	CFAP61	white wine liking

Defining White Wine Liking

White wine liking is fundamentally a complex human preference, representing an individual’s subjective appreciation and positive hedonic response to white wine.^[1] This trait is conceptualized as a specific instance within the broader domain of “food liking,” which encompasses an individual’s overall enjoyment and preference for various food and beverage items.^[1]While white wine liking holds significant cultural and societal importance and has been extensively studied, the precise molecular and sensory mechanisms that underpin this specific preference, and food liking in general, continue to be areas of active scientific investigation.^[1] It reflects a composite trait influenced by both direct sensory perceptions (taste, aroma, mouthfeel) and cognitive evaluations.

Assessment and Methodologies

The operational definition of white wine liking typically involves quantitative self-reporting through structured questionnaires.^[1] Participants are asked to rate their liking for white wine using psychometric scales, such as a 9-point scale ranging from “dislike extremely”.^[2] to “like extremely” commonly employed in studies involving European populations.^[1] To accommodate diverse linguistic backgrounds or literacy levels, alternative assessment tools, like a 5-point scale incorporating smiley faces, are utilized, particularly in populations where direct numerical interpretation might be challenging.^[1] To ensure comparability of data collected using different scales, all raw scores are systematically standardized by dividing each participant’s rating by the maximum number of categories available on the specific scale used.^[1] This process yields a “standardized wine liking” score, which serves as the primary dependent variable in statistical analyses, often within mixed model linear regression frameworks that adjust for covariates such as age and sex.^[1]

Genetic and Phenotypic Classifications

White wine liking can be dimensionally classified by its association with specific genetic markers, revealing a significant genetic component to this preference.^[1]A notable genetic locus associated with white wine liking is thers9276975 :C4T polymorphism, located within the 3′-UTR region of the HLA-DOA gene.^[1] This SNP’s position suggests a regulatory rather than a direct functional role for HLA-DOA, which encodes a non-canonical MHC class II molecule involved in the modulation of other MHC class II proteins.^[1] The observed association for rs9276975 :C4T achieved genome-wide significance with a P-value of 2.1 × 10−8, establishing HLA-DOA as a key genetic contributor to white wine preference.^[1]Further phenotypic classification reveals distinct patterns based on sex, with the genetic association between white wine liking andHLA-DOA demonstrating a significantly stronger effect in women (P = 1 × 10−7) compared to men (P = 0.01).^[1]Women exhibit approximately twice the effect size (0.067 versus 0.033).^[1] This sex-specific difference lends support to the “olfactory hypothesis,” which posits that HLA-DOA may modulate the perception of specific volatile compounds integral to wine flavor, consistent with documented differences in olfactory sensitivity between sexes.^[1] While other genes like OR7D4, SCNN1D, OR2J3, and TAS1R2 have been linked to various chemosensory perceptions, the association of HLA-DOAappears specific to white wine liking, distinguishing it from general food preferences.^[1]

The nomenclature surrounding white wine liking encompasses terms essential for its and genetic analysis. “Wine-liking ascertainment” describes the methodological process of collecting individual preference data, while “standardized wine liking” refers to the normalized scores used to ensure data comparability across diverse cohorts.^[1]In the genetic context, “Single Nucleotide Polymorphism” (SNP) is a fundamental term, exemplified byrs92769775 :C4T, which represents a specific variation in the DNA sequence.^[1] The gene symbol HLA-DOA identifies the Human Leukocyte Antigen DOA gene, a key genetic locus implicated in white wine preference.^[1]Statistical terms such as “P-value” and “Beta” (representing effect size) are critical for quantifying the significance and magnitude of genetic associations.^[1]White wine liking is conceptually related to broader “chemosensory traits,” which include the perception of taste, smell, and mouthfeel, all contributing to the overall flavor experience.^[1]While sharing commonalities with “red wine liking,” the specific genetic underpinnings and strength of associations may differ between these two wine preferences.^[1]The concept of “olfaction,” or the sense of smell, is a particularly pertinent related trait, as the genetic influence on white wine liking is hypothesized to operate through the modulation of volatile compound perception, an area where sex-specific sensitivities have been observed.^[1]

Sensory Receptor Activation and Initial Signaling

The perception of white wine liking begins with the activation of various sensory receptors that detect the complex array of chemical compounds present in wine. This initial phase involves both gustatory (taste) and olfactory (smell) pathways, which contribute to the overall flavor experience.^[3] For instance, ethanol flavor perception, distinct from taste, has been linked to variants in the olfactory receptor gene OR7D4 and SCNN1D, a gene encoding a subunit of the salt taste receptor.^[2] Similarly, a variant in the OR2J3 olfactory receptor gene has been shown to impair the ability to detect cis-3-hexen-1-ol, a significant volatile compound found in wine.^[4] These receptor activations trigger intracellular signaling cascades, translating chemical stimuli into neural signals that form the foundational input for the brain’s interpretation of white wine attributes.

HLA-DOA Mediated Olfactory Modulation and Regulatory Feedback

A significant pathway influencing white wine liking involves theHLA-DOA gene, which encodes a non-canonical Major Histocompatibility Complex (MHC) class II molecule.^[1] This molecule plays a crucial regulatory role within the immune system by inhibiting HLA-DM, another non-canonical MHC class II molecule, thereby preventing the general activation of MHC class II molecules.^[1] Concurrently, HLA-DOA also activates other MHC class II proteins by decoupling from the CLIP protein, which is essential for their specific binding to antigens.^[1] It is hypothesized that HLA-DOA, through its regulation of MHC class II molecules, modulates the perception of specific volatile compounds found in wine, likely interacting directly with the olfactory epithelium.

Genetic Regulatory Mechanisms and Immune-Sensory Crosstalk

The rs9276975 :C>T polymorphism, located in the 3’-UTR region of the HLA-DOAgene, suggests a regulatory role in white wine liking.^[1] This genetic variation likely influences HLA-DOA gene expression or post-transcriptional regulation, thereby impacting its functional contribution to MHC class II regulation and, consequently, olfactory perception. This mechanism exemplifies systems-level integration and pathway crosstalk, where components traditionally associated with the immune system, such as MHC molecules, interact with and influence the sensory system.^[1] The observed stronger association of HLA-DOAwith white wine liking in women, exhibiting twice the effect size compared to men, further highlights complex regulatory interactions, potentially involving sex-specific differences in olfactory sensitivity and hormonal influences.^[1]

Integrated Perception, Contextual Influences, and Emergent Liking

The ultimate experience of white wine liking is an emergent property resulting from the hierarchical regulation and integration of various sensory and regulatory pathways within the brain. The initial activations of olfactory and gustatory receptors, coupled with the modulatory influence ofHLA-DOA on olfactory processing, culminate in a complex sensory profile. This integrated perception is further shaped by contextual factors, such as the specific composition of white wine (e.g., lower tannin content compared to red wine), which allows the olfactory components to be more prominent.^[1] Understanding these intricate interactions provides insight into the molecular bases underlying food liking and choice, underscoring the broad biological significance of these pathways in shaping individual preferences.

Population-Level Prevalence and Demographic Correlates

Population-level studies on white wine liking reveal variations in its prevalence and significant demographic influences across different groups. A comprehensive genome-wide association study, encompassing five isolated populations from Europe and Central Asia, identified distinct mean liking ratings across these groups.^[1]For instance, the ERF (Erasmus Rucphen Family) cohort, originating from the Netherlands, reported the lowest mean white wine liking compared to the Italian and Central Asian populations studied, highlighting inherent differences in preference patterns that may be shaped by cultural, environmental, or genetic factors prevalent within specific geographic and ancestral groups.^[1]Furthermore, demographic analysis uncovered a notable sex-specific association with white wine liking. A genetic variant,rs9276975 , located in the HLA-DOAgene, showed a significantly stronger association with white wine liking in women compared to men.^[1]Specifically, women exhibited an effect size twice as large as men (0.067 vs. 0.033), with a P-value of 1 × 10−7 in women versus 0.01 in men.^[1] This pronounced difference suggests that biological factors, potentially related to olfactory sensitivity where women are often described as more perceptive to certain odors, may play a crucial role in shaping individual preferences for white wine.^[1]

Cross-Population Genetic Landscape of Liking

Cross-population comparisons are critical for understanding the generalizability and population-specific nuances of white wine liking. The study leveraged five distinct isolated populations: three Italian cohorts (INGI-CARL, INGI-FVG, INGI-VB), the Dutch ERF cohort, and the diverse Silk Road (SR) cohort comprising individuals from communities across five Central Asian nations.^[1] While mean liking ratings varied across these geographically and ancestrally distinct groups, the primary association of rs9276975 in HLA-DOAwith white wine liking was consistently observed and replicated across these diverse populations, underscoring its potential broad relevance.^[1] This multi-ethnic approach provided valuable insights into how genetic predispositions might manifest across different human populations, despite observed differences in overall preference levels.

However, cross-population analyses also highlighted instances of population-specific genetic effects. For example, a previous association between white wine and a variant in the TAS1R2 gene, identified in Central Asian populations, did not replicate in the combined meta-analysis of the current study, yielding a non-significant P-value of 0.83.^[1] This lack of replication across European and Central Asian cohorts suggests the possibility of allelic heterogeneity, where different genetic variants or underlying mechanisms might contribute to the trait in distinct populations, necessitating further research to elucidate these population-specific genetic architectures.^[1]

Study Methodologies and Large-Scale Cohort Insights

Understanding white wine liking at a population level relies on robust epidemiological methodologies and the utilization of large-scale cohort studies. This research employed a genome-wide association study (GWAS) design, initially performing a discovery phase on approximately 2271 samples from three Italian isolated populations, followed by a replication phase involving 1261 samples from the Dutch ERF study and 335 samples from the Central Asian SR cohort, totaling 3885 individuals.^[1] The use of genetically isolated populations, such as the ERF cohort which traces descendants from 22 couples, offers advantages for genetic studies by reducing genetic heterogeneity and increasing power to detect associations.^[1]White wine liking was assessed through questionnaires, utilizing different rating scales (1-9 points for European populations, 5-point scale with smiley faces for the SR cohort to overcome linguistic barriers), which were subsequently standardized to ensure comparability across diverse populations.^[1] Methodologically, association analyses were conducted using mixed model linear regression, incorporating sex and age as covariates and a kinship matrix to account for genetic relatedness within cohorts, thereby minimizing false positives due to population structure.^[1] Meta-analysis techniques, including inverse-variance weighting and z-score based methods, were applied to combine results from discovery and replication cohorts, confirming the robustness of the primary genetic association.^[1] While the study achieved sufficient statistical power to detect associations, the focus on isolated populations, though advantageous for genetic discovery, necessitates careful consideration of representativeness and generalizability when extrapolating findings to broader, more genetically diverse global populations.^[1]

Frequently Asked Questions About White Wine Liking

These questions address the most important and specific aspects of white wine liking based on current genetic research.

1. Why do I love white wine, but my sibling hates it?

Your genes play a big role in your preferences. A specific genetic variation in the HLA-DOAgene is strongly linked to white wine liking, and you and your sibling might have different versions of this gene. Other genes, likeTAS1R2 related to sweet perception, can also influence how you experience wine, leading to diverse preferences even within families.

2. Do women generally like white wine more than men?

It appears that genetic factors influencing white wine liking can have a stronger effect in women. The specific genetic variation in theHLA-DOA gene linked to liking white wine shows an effect that is twice as strong in women compared to men. This might be partly because women are often more sensitive to certain smells.

3. Does my sense of smell decide if I like white wine?

Yes, your sense of smell is very important! It’s thought that a gene called HLA-DOAmight influence your white wine liking by changing how you perceive specific scents or volatile compounds in the wine. These compounds are often produced by bacteria during winemaking, and your genetics can tune your ability to detect and appreciate them.

4. Does my family’s ethnic background influence my white wine preference?

Your ancestry can play a role. Studies have shown that genetic associations with white wine liking, such as variations in theTAS1R2 gene, might be more common or have different effects in specific populations, like those from Central Asia, compared to European populations. This means your genetic background can influence how you perceive and enjoy white wine.

5. Does liking white wine mean I’ll like all foods?

Not necessarily. The genetic link identified for white wine liking, involving theHLA-DOA gene, seems to be specific to wine and not a general factor for liking other foods or beverages. While other genes might influence broader taste or smell preferences, this particular association is quite focused on wine.

6. Could a genetic test tell me if I’m likely to enjoy white wine?

Yes, in theory, a genetic test could provide some insight. Researchers have identified a specific genetic variant, rs9276975 , in the HLA-DOAgene that is significantly associated with white wine liking. Knowing your version of this variant could indicate a predisposition, but personal preference is still complex.

7. Is my immune system somehow involved in whether I enjoy white wine?

Surprisingly, yes, there’s a hypothesis for that! The HLA-DOAgene, which is strongly linked to white wine liking, encodes a molecule involved in regulating your immune system’s MHC class II molecules. It’s thought that this gene might indirectly affect your ability to perceive specific volatile compounds in wine, which are often produced by bacteria.

8. Why do some white wines taste sweeter to me than others?

Your perception of sweetness in white wine can be influenced by your genetics, specifically variations in genes like TAS1R2, which encodes a sweet taste receptor. Different versions of this gene can alter how intensely you perceive sweetness, contributing to your unique preferences for various white wines.

9. Could winemakers use genetics to make me like their wine more?

Potentially, yes. Understanding the genetic factors that influence wine liking, like the role of the HLA-DOA gene and its effect on perceiving volatile compounds, could inform the wine industry. This knowledge might guide efforts to improve production methods or tailor wine flavors to better suit consumer preferences based on genetic insights.

10. Does liking white wine mean I’ll like other alcohol?

Not necessarily for all types of alcohol. While some genes like TAS1R2 have been linked to liking both white wine and vodka in some populations, the strong genetic association found for HLA-DOA seems specific to wine liking. Your preference for other alcoholic drinks might involve different genetic or environmental factors.

This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.

Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.

References

[1] Pirastu, N., 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, vol. 23, no. 10, 2015, pp. 1391–1396.

[2] Knaapila, A., et al. “Genetic analysis of chemosensory traits in human twins.” Chem Senses, vol. 37, 2012, pp. 869–881.

[3] Polásková, P., et al. “Wine ﬂavor: chemistry in a glass.” Chem Soc Rev, vol. 37, 2008, pp. 2478–2489.

[4] McRae, J. F., et al. “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, vol. 37, 2012, pp. 585–593.