Genome-wide association meta-analysis identifies two novel loci associated with dental caries.

BACKGROUND: Tooth loss significantly impacts oral function and overall health deterioration. Dental caries and periodontal disease are major contributors to tooth loss, emphasizing the critical need to prevent these conditions. Genetic studies have played a crucial role in deepening our understanding of the underlying mechanisms of these diseases. While large-scale genome-wide association studies (GWAS) on dental caries and periodontal disease have been conducted extensively, research focusing on Asian populations remains limited. Given substantial genetic and lifestyle variations across ethnicities, conducting studies across diverse populations is imperative. This study aimed to uncover new insights into the genetic mechanisms of these diseases, contributing to broader knowledge and potential targeted interventions. METHODS: We conducted a GWAS using genome data from 45,525 Japanese individuals, assessing their self-reported history of dental caries and periodontal disease. Additionally, we performed a meta-analysis by integrating our results with those from a previous large-scale GWAS predominantly involving European populations. RESULTS: While no new loci associated with periodontal disease were identified, we discovered two novel loci associated with dental caries. The lead variants of these loci were intron variant rs10974056 in GLIS3 and intron variant rs4801882 in SIGLEC5. CONCLUSION: Our study findings are anticipated to advance understanding of the underlying mechanisms of dental caries and periodontal disease. Thes insights may inform better management strategies for patients affected by these conditions.

Strong association between the 12q24 locus and sweet taste preference in the Japanese population revealed by genome-wide meta-analysis.

The sweet taste preference of humans is an important adaptation to ensure the acquisition of carbohydrate nutrition; however, overconsumption of sweet foods can potentially lead to diseases such as obesity and diabetes. Although previous studies have suggested that interindividual variation of human sweet taste preference is heritable, genetic loci associated with the trait have yet to be fully elucidated. Here, we genotyped 12,312 Japanese participants using the HumanCore-12+ Custom BeadChip or the HumanCore-24 Custom BeadChip microarrays. The sweet taste preference of the participants was surveyed via an internet-based questionnaire, resulting in a five-point scale of sweet taste preference. The genome-wide meta-analysis of the Japanese participants revealed a strong association between the 12q24 locus and sweet taste preference scale (P = 2.8 × 10-70). The lead variant rs671 is monoallelic in non-East Asian populations and is located in the aldehyde dehydrogenase (ALDH2) gene, encoding an enzyme involved in alcohol metabolism. The association between the minor allele of rs671 and sweet taste preference was attenuated by adjusting for alcohol drinking. The subgroup analysis showed that the effect of rs671 on sweet taste preference was greater in males than in females. In conclusion, we found an association between the 12q24 locus and sweet taste preference in the Japanese population, and showed that the adjustment for drinking habits attenuated the association. This novel genetic association may provide new clues to elucidate mechanisms determining sweet taste preferences.

GWAS of habitual coffee consumption reveals a sex difference in the genetic effect of the 12q24 locus in the Japanese population.

BACKGROUND: Studies on genetic effects of coffee consumption are scarce for Asian populations. We conducted a genome-wide association study (GWAS) of habitual coffee consumption in Japan using a self-reporting online survey. RESULTS: Candidate genetic loci associated with habitual coffee consumption were searched within a discovery cohort (N = 6,264) and confirmed in a replication cohort (N = 5,975). Two loci achieved genome-wide significance (P < 5 × 10- 8) in a meta-analysis of the discovery and replication cohorts: an Asian population-specific 12q24 (rs79105258; P = 9.5 × 10- 15), which harbors CUX2, and 7p21 (rs10252701; P = 1.0 × 10- 14), in the upstream region of the aryl hydrocarbon receptor (AHR) gene, involved in caffeine metabolism. Subgroup analysis revealed a stronger genetic effect of the 12q24 locus in males (P for interaction = 8.2 × 10- 5). Further, rs79105258 at the 12q24 locus exerted pleiotropic effects on body mass index (P = 3.5 × 10- 4) and serum triglyceride levels (P = 8.7 × 10- 3). CONCLUSIONS: Our results consolidate the association of habitual coffee consumption with the 12q24 and 7p21 loci. The different effects of the 12q24 locus between males and females are a novel finding that improves our understanding of genetic influences on habitual coffee consumption.

A genome-wide association study on photic sneeze syndrome in a Japanese population.

Photic sneeze syndrome (PSS) is characterized by a tendency to sneeze when the eye is exposed to bright light. Recent genome-wide association studies (GWASs) have identified single-nucleotide polymorphisms (SNPs) associated with PSS in Caucasian populations. We performed a GWAS on PSS in Japanese individuals who responded to a web-based survey and provided saliva samples. After quality control, genotype data of 210,086 SNPs in 11,409 individuals were analyzed. The overall prevalence of PSS was 3.2%. Consistent with previous reports, SNPs at 3p12.1 were associated with PSS at genome-wide significance (p < 5.0 × 10-8). Furthermore, two novel loci at 9q34.2 and 4q35.2 reached suggestive significance (p < 5.0 × 10-6). Our data also provided evidence supporting the two additional SNPs on 2q22.3 and 9q33.2 reportedly associated with PSS. Our study reproduced previous findings in Caucasian populations and further suggested novel PSS loci in the Japanese population.

A web-based genome-wide association study reveals the susceptibility loci of common adverse events following COVID-19 vaccination in the Japanese population.

The coronavirus disease 2019 (COVID-19) pandemic has spread rapidly worldwide. To prevent its spread, mRNA-based vaccines made by Pfizer/BioNTech (BNT162b1) and Moderna (mRNA-1273) have been widely used, including in Japan. Various adverse events have been reported following the COVID-19 mRNA vaccination, with differences observed among individuals. However, analyses of the genetic background associated with the susceptibility to side effects have been limited. In the present study, we performed genome-wide association studies (GWAS) for self-reported adverse events of the COVID-19 mRNA vaccination in 4545 Japanese individuals and identified 14 associated loci. Among these, 6p21 was associated with 37.5 °C or higher fever, 38 °C or higher fever, and muscle pain. HLA allele association analysis revealed that various HLA alleles were associated with the adverse effects; HLA-DQA1*03:01 and HLA-A*11:01 were more reliably associated with the adverse effects. Our results may enable the preparation and management of adverse effects by identifying the susceptibility to these adverse events. Furthermore, we obtained valuable data that may lead to a better understanding of the mechanisms of action of the COVID-19 mRNA vaccines.

Psychological Distress and Personality Dimensions Associated with Romantic Orientation Among Japanese Adults.

Purpose: Evidence is scarce regarding the associations of romantic orientation with mental health and personality. The aims of the present study, therefore, were to examine psychological distress among homoromantic, biromantic, and heteroromantic adults and to investigate how personality dimensions influence their distress. Methods: A cross-sectional survey study was conducted between August 2018 and January 2021. Psychological distress, personality, and romantic orientation were assessed with the 6-item Kessler Psychological Distress Scale (K6), the Ten-Item Personality Inventory (TIPI), and a question about romantic orientation, respectively, in a web-based survey distributed to 11,922 participants. Saliva samples were collected for DNA extraction. After excluding those who did not cluster with Japanese ancestry and those whose genotypic sex did not match their reported sex, 11,662 individuals were included in further analyses. Results: The prevalence of being homoromantic or biromantic was 1.0% and 2.0% for females and 1.5% and 1.2% for males, respectively. Homoromantic males, but not females, had significantly higher K6 scores than their heteroromantic counterparts. Both male and female biromantic participants had significantly higher K6 scores than their heteroromantic counterparts. Furthermore, a significant association was found between romantic orientation and TIPI scores. Accounting for personality profiles did not alter the observed association between romantic orientation and psychological distress. Conclusion: Biromantic adults and homoromantic male adults of genetically confirmed Japanese ancestry living in Japan experienced higher psychological distress than heteroromantic individuals. The mental health disparities of the romantic minority individuals were irrespective of their personality profiles, suggesting the involvement of other factors such as minority stress in Japan.

Association between Dietary Behaviors and BMI Stratified by Sex and the ALDH2 rs671 Polymorphism in Japanese Adults.

The rs671 polymorphism, unique to East Asians, is well known to change the sensitivity to alcohol. Moreover, this polymorphism is associated not only with alcohol intake but also with several dietary behaviors (DBs), chronic diseases, and BMI, but the triadic association among the rs671 genotype, DBs, and BMI is unclear. This study included 12,271 Japanese subjects and aimed to observe this three-way association using the rs671 polymorphism, data of 56 DBs, and BMI. All analyses were stratified by participant sex. First, linear regression analyses resulted in significant associations between 18 and 21 DBs and BMI in males and females, respectively. Next, genetic heterogeneity was observed in all sub-groups via interaction analysis of the rs671 genotype stratified by drinking habits. Finally, we observed the characteristics of BMI-related DBs based on the rs671 genotype via stepwise regression analyses stratified by the rs671 genotype and drinking habits. Notably, positive associations were observed between lactobacillus beverage intake and BMI among participants with the rs671 polymorphism AA genotype in both sexes. This study suggests that the rs671 polymorphism modifies the association between DBs and BMI independently of drinking habits, providing evidence for the potential use of rs671 polymorphism information for precision nutrition with East Asians.

Carrot Consumption Frequency Associated with Reduced BMI and Obesity through the SNP Intermediary rs4445711.

It is unclear whether genetic interactions are involved in the association between vegetable intake and reduced body mass index (BMI) or obesity. We conducted a comprehensive search for single nucleotide polymorphisms (SNPs) which are associated with the interaction between vegetable intake frequency and BMI or obesity. We performed a genome-wide association analysis to evaluate the genetic interactions between self-reported intake of vegetables such as carrot, broccoli, spinach, other green vegetables (green pepper and green beans), pumpkin, and cabbage with BMI and obesity, which is defined as a BMI ≥ 25.0 kg/m2 in the Japanese population (n = 12,225). The mean BMI and prevalence of obesity was 23.9 ± 3.4 kg/m2 and 32.3% in men and 22.1 ± 3.8 kg/m2 and 17.3% in in women, respectively. A significant interaction was observed between rs4445711 and frequency of carrot intake on BMI (p = 4.5 × 10-8). This interaction was slightly attenuated after adjustment for age, sex, alcohol intake, smoking, physical activity and the frequency of total vegetable intake (p = 2.1 × 10-7). A significant interaction was also observed between rs4445711 and frequency of carrot intake on obesity (p = 2.5 × 10-8). No significant interactions that were the same as the interaction between frequency of carrot intake and rs4445711 were observed between the intake frequency of broccoli, spinach, other green vegetables, pumpkin or cabbage and BMI or obesity. The frequency of carrot consumption is implicated in reducing BMI by the intermediary of rs4445711. This novel genetic association may provide new clues to clarify the association between vegetable intake and BMI or obesity.

A Genome-Wide Association Study Identifies the Association between the 12q24 Locus and Black Tea Consumption in Japanese Populations.

Several genome-wide association studies (GWASs) have reported the association between genetic variants and the habitual consumption of foods and drinks; however, no association data are available regarding the consumption of black tea. The present study aimed to identify genetic variants associated with black tea consumption in 12,258 Japanese participants. Data on black tea consumption were collected by a self-administered questionnaire, and genotype data were obtained from a single nucleotide polymorphism array. In the discovery GWAS, two loci met suggestive significance (p < 1.0 × 10-6). Three genetic variants (rs2074356, rs144504271, and rs12231737) at 12q24 locus were also significantly associated with black tea consumption in the replication stage (p < 0.05) and during the meta-analysis (p < 5.0 × 10-8). The association of rs2074356 with black tea consumption was slightly attenuated by the additional adjustment for alcohol drinking frequency. In conclusion, genetic variants at the 12q24 locus were associated with black tea consumption in Japanese populations, and the association is at least partly mediated by alcohol drinking frequency.

Food allergy is associated with depression and psychological distress: A web-based study in 11,876 Japanese.

BACKGROUND: Although some studies suggest a possible association between food allergy (FA) and depression/psychological distress, empirical data are still scarce. We aimed to examine whether this association exists in a large sample of the Japanese population. METHODS: This web-based cross-sectional survey included 1000 individuals with self-reported lifetime history of clinical depression (mean age: 41.4 years, 501 men), and the remaining 10,876 subjects served as controls (mean age: 45.1 years, 5691 men). A six-item Kessler scale (K6) test was used to evaluate severe psychological distress. Information on FA was obtained by a self-report checking for 27 specific allergens. RESULTS: Participants with FA, 2 or more, 3 or more, and 4 or more allergens were more common in the depression group than in the control group (odds ratio [OR] = 1.64, 1.75, 2.02, and 2.27, respectively; p < 0.001). In the allergen analyses, allergies for shrimp, egg, mackerel, crab, kiwi fruit, milk, banana, and squid (nominal, p < 0.05) were more common in the depression group than in the controls. The proportion of individuals who had a K6 test cut-off score ≥ 13 was higher in the FA group than in the non-FA group, in the total sample (OR = 1.32, 1.62, 2.04 and 2.51; 1, 2, 3, and 4 or more allergens, respectively; p < 0.001). LIMITATIONS: The identification of FA and depression was based on self-reports. CONCLUSIONS: Our data suggest that FA is a risk factor for depression and severe psychological distress, which depends on the number of allergens.

Possible association between photic sneeze syndrome and migraine and psychological distress.

BACKGROUND: Photic sneeze syndrome (PSS) is a condition that causes sneezing when the eye is exposed to sudden bright light. Because alterations in the parasympathetic and trigeminal nerve systems have been implicated in PSS, and such systems are involved in migraine and stress-related disorders, we examined the possible associations of PSS with migraine and psychological distress. METHODS: The presence of PSS and migraine was examined in 11 840 participants from the general population using a self-report questionnaire. Psychological distress was assessed by the 6-item Kessler Psychological Distress Scale (K6). RESULTS: The overall prevalence of PSS was 3.1%. Individuals with PSS were more likely to suffer from migraine (odds ratio = 1.97, P = 2.18 × 10-9 ), clinically relevant psychological distress (K6 score ≥ 5: odds ratio = 1.40, P = 0.00143), and severe psychological distress (K6 score ≥ 13: odds ratio = 1.49, P = 0.0486). Overall, K6 scores were significantly higher in those with PSS than in those without (P = 0.000013). Analysis controlling for sex and the presence of migraine showed that PSS was associated with higher K6 scores irrespective of sex or the presence of migraine. CONCLUSIONS: The low prevalence of PSS identified in the present study may be due to the inadequate ability of the self-report questionnaire to identify PSS. Despite such limitation, the present study suggests that individuals with PSS are more likely to suffer from migraine and psychological distress than those without PSS. PSS may be a potential target for the research of migraine and stress-related disorders.

Genome-wide association study identifies a novel locus associated with psychological distress in the Japanese population.

Major depressive disorder (MDD) is a common and disabling psychiatric disorder. A recent mega analysis of genome-wide association studies (GWASs) identified 44 loci associated with MDD, though most of the genetic etiologies of the MDD/psychological distress remain unclear. To further understand the genetic basis of MDD/psychological distress, we conducted a GWAS in East Asia with more than 10,000 participants of Japanese ancestry who had enrolled in a direct-to-consumer genetic test. After quality control on the genotype data, 10,330 subjects with a total of 8,567,708 imputed SNPs were eligible for the analysis. The participants completed a self-administered questionnaire on their past medical history and health conditions that included the 6-item Kessler screening scale (K6 scale) for psychological distress (cut-off point of 5) and past medical history of MDD, resulting in 3981 subjects assigned to "psychologically distressed group" [cases], and the remaining 6349 subjects were assigned to the "non-psychologically distressed group" [controls]. In this GWAS, we found an association with genome-wide significance at rs6073833 (P = 7.60 × 10-9) in 20q13.12. This is, to the best of our knowledge, the first large-scale GWAS for psychological distress using data from direct-to-consumer (DTC) genetic tests in a population of non-European-ancestry, and the present study thus detected a novel locus significantly associated with psychological distress in the Japanese population.

Identification of the 12q24 locus associated with fish intake frequency by genome-wide meta-analysis in Japanese populations.

BACKGROUND: Japan is traditionally a country with one of the highest levels of fish consumption worldwide, although the westernization of the Japanese diet has resulted in the reduction of fish consumption. A recent meta-analysis of genome-wide association studies (GWASs) on Western populations has identified a single nucleotide polymorphism (SNP) associated with fish intake frequency. Here, we examined the genetic basis for fish intake frequency among Japanese individuals. RESULTS: We conducted a meta-analysis of a GWAS including 12,603 Japanese individuals and identified a susceptibility locus for fish intake frequency at 12q24 (lead variant was rs11066015, P = 5.4 × 10-11). rs11066015 was in a strong linkage disequilibrium with rs671, a well-known SNP related to alcohol metabolism. When adjusted for alcohol drinking, the association between rs11066015 and fish intake frequency was substantially attenuated. Subgroup analysis revealed that the effect of the 12q24 variant on fish intake frequency was stronger in males than in females (P for interaction = 0.007) and stronger in the older subgroup than in the younger subgroup (P for interaction = 0.006). CONCLUSIONS: Our findings suggest that the 12q24 locus is associated with fish intake frequency via alcohol drinking. This study can help contribute to personalized nutrition information, suggesting that fish intake should be promoted to consumers who have the rs11066015 minor allele, which is genetically linked to low fish intake frequency, especially in male and older individuals.