RETRACTED: The plant is neither dumb nor deaf; it talks and hears.

Animals and insects communicate using vibrations that are frequently too low or too high for human ears to detect. Plants and trees can communicate and sense sound. Khait et al. used a dependable recording system to capture airborne sounds produced by stressed plants. In addition to allowing plants to communicate their stress, sound aids in plant defense, development, and resilience. It also serves as a warning that danger is approaching. Demey et al. and others discussed the audit examinations that were conducted to investigate sound discernment in plants at the atomic and biological levels. The biological significance of sound in plants, the morphophysiological response of plants to sound, and the airborne noises that plants make and can hear from a few meters away were all discussed.

Interactions Between Serotonin Transporter Gene and Adverse Childhood Experience in a Generalized Additive Model: A Pilot Study.

BACKGROUND: While most people experience potentially traumatic events (PTEs), including Adverse Childhood Experiences (ACEs), the stress reactions to PTEs on mental health outcomes are highly heterogeneous. Resilience is influenced by a complex biopsychosocial ecological system, including gene serotonin transporter-linked promoter region or 5-HTTLPR /rs25531 by ACEs interactions. AIMS: This pilot study investigated the gene-by-environment interactions on mental health outcomes in adults enrolled in a health care profession program using a generalized additive model (GAM). METHODS: Seventy health care college students (mean age = 27.4 years, 67.1% women) participated in this cross-sectional study. Saliva samples were collected from students to analyze 5-HTTLPR/rs25531. Participants completed the ACE Questionnaire and the Mental Health Inventory. GAMs with different interaction terms were built adjusting for age, gender, and race. The value of the effective degree of freedom (EDF) quantifies the curvature of the relationship. RESULTS: Among participants with the long allele of 5-HTTLPR/rs25531, a linear pattern was found between the total ACE score and mental health outcomes (EDF = 1). Conversely, among participants with the short allele, EDF was approximately 2, indicating a curved association suggesting that mental health worsens in individuals exposed to up to four types of ACEs. CONCLUSIONS: The impact of up to four ACEs on mental health was stronger among individuals with the short allele of 5-HTTLPR/rs25531 than those with the long allele. Although this study does not claim to provide a definite approach to analyzing gene-by-environment interactions, we offer a different perspective to explore the relationship.

Population-Based Impact of Smoking, Drinking, and Genetic Factors on HDL-cholesterol Levels in J-MICC Study Participants.

BACKGROUND: Environmental and genetic factors are suggested to exhibit factor-based association with HDL-cholesterol (HDL-C) levels. However, the population-based effects of environmental and genetic factors have not been compared clearly. We conducted a cross-sectional study using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study to evaluate the population-based impact of smoking, drinking, and genetic factors on low HDL-C. METHODS: Data from 11,498 men and women aged 35-69 years were collected for a genome-wide association study (GWAS). Sixty-five HDL-C-related SNPs with genome-wide significance (P < 5 × 10-8) were selected from the GWAS catalog, of which seven representative SNPs were defined, and the population-based impact was estimated using population attributable fraction (PAF). RESULTS: We found that smoking, drinking, daily activity, habitual exercise, egg intake, BMI, age, sex, and the SNPs CETP rs3764261, APOA5 rs662799, LIPC rs1800588, LPL rs328, ABCA1 rs2575876, LIPG rs3786247, and APOE rs429358 were associated with HDL-C levels. The gene-environmental interactions on smoking and drinking were not statistically significant. The PAF for low HDL-C was the highest in men (63.2%) and in rs3764261 (31.5%) of the genetic factors, and the PAFs of smoking and drinking were 23.1% and 41.8%, respectively. CONCLUSION: The present study showed that the population-based impact of genomic factor CETP rs3764261 for low HDL-C was higher than that of smoking and lower than that of drinking.

SERPINE1 mRNA Binding Protein 1 Is Associated with Ischemic Stroke Risk: A Comprehensive Molecular-Genetic and Bioinformatics Analysis of SERBP1 SNPs.

The SERBP1 gene is a well-known regulator of SERPINE1 mRNA stability and progesterone signaling. However, the chaperone-like properties of SERBP1 have recently been discovered. The present pilot study investigated whether SERBP1 SNPs are associated with the risk and clinical manifestations of ischemic stroke (IS). DNA samples from 2060 unrelated Russian subjects (869 IS patients and 1191 healthy controls) were genotyped for 5 common SNPs-rs4655707, rs1058074, rs12561767, rs12566098, and rs6702742 SERBP1-using probe-based PCR. The association of SNP rs12566098 with an increased risk of IS (risk allele C; p = 0.001) was observed regardless of gender or physical activity level and was modified by smoking, fruit and vegetable intake, and body mass index. SNP rs1058074 (risk allele C) was associated with an increased risk of IS exclusively in women (p = 0.02), non-smokers (p = 0.003), patients with low physical activity (p = 0.04), patients with low fruit and vegetable consumption (p = 0.04), and BMI ≥25 (p = 0.007). SNPs rs1058074 (p = 0.04), rs12561767 (p = 0.01), rs12566098 (p = 0.02), rs6702742 (p = 0.036), and rs4655707 (p = 0.04) were associated with shortening of activated partial thromboplastin time. Thus, SERBP1 SNPs represent novel genetic markers of IS. Further studies are required to confirm the relationship between SERBP1 polymorphism and IS risk.

rs2671655 single nucleotide polymorphism modulates the risk for gastric cancer in Helicobacter pylori-infected individuals: a genome-wide association study in the Korean population.

OBJECTIVE: To identify genetic variations which is associated with gastric cancer (GC) risk according to Helicobacter pylori infection. METHODS: This study incorporated 527 GC patients and 441 controls from a cohort at Seoul National University Bundang Hospital. The associations between GC risk and single nucleotide polymorphisms were calculated, stratified by H. pylori status, adjusting for age, sex, and smoking. mRNA expression from non-cancerous gastric mucosae was evaluated using reverse transcription quantitative polymerase chain reaction. RESULTS: In the entire cohort, genome-wide association study showed no significant variants reached the genome-wide significance level. In the H. pylori-positive group, rs2671655 (chr17:47,468,020;hg19, GH17J049387 enhancer region) was identified at a genome-wide significance level, which was more pronounced in diffuse type GC. There was no significant variant in the H. pylori-negative group, indicating the effect modification of rs2671655 by H. pylori. Among the target genes of GH17J049387 enhancer (PHB1, ZNF652 and SPOP), PHB1 mRNA was expressed more in cases than in controls, who were not affected by H. pylori. By contrast, an increase in ZNF652 and SPOP in GC was observed only in the H. pylori-negative group (P < 0.05). Mediation analysis showed that PHB1 (P = 0.0238) and SPOP (P = 0.0328) mediated the effect of rs2671655 on GC risk. The polygenic risk score was associated with the number of rs2671655 risk alleles only in the H. pylori-positive group (P = 0.0112). CONCLUSION: After H. pylori infection, rs2671655 may increase GC risk, especially in diffuse-type GC, by regulating the expression of several genes that consequently modify susceptibility to GC.

Ambient Air Pollutants and Traffic Factors Were Associated with Blood and Urine Biomarkers and Asthma Risk.

The UK Biobank (UKBB) is a large population-based cohort that provides a unique opportunity to study the association between environmental exposure and biomarkers and to identify biomarkers as potential instruments for assessing exposure dose, health damage, and disease risks. On 462 063 participants of European ancestry, we characterized the relationship of 38 disease-relevant biomarkers, asthma diagnosis, ambient pollution, traffic factors, and genetic background. The air pollutant exposure on the UKBB cohort was fairly low (e.g., mean PM2.5 concentration at 10.0 µg/m3). Nevertheless, 30 biomarkers were in association with at least one environmental factor; e.g., C-reactive protein levels were positively associated with NO (padj = 2.99 × 10-4), NO2 (padj = 4.15 × 10-4), and PM2.5 (padj = 1.92 × 10-6) even after multiple testing adjustment. Asthma diagnosis was associated with four pollutants (NO, NO2, PM2.5, and PM10). The largest effect size was observed in PM2.5, where a 5 µg/m3 increment of exposure was associated with a 1.52 increase in asthma diagnosis (p = 4.41 × 10-13). Further, environmental exposure and genetic predisposition influenced biomarker levels and asthma diagnosis in an additive model. The exposure-biomarker associations identified in this study could serve as potential indicators for environmental exposure induced health damages. Our results also shed light on possible mechanisms whereby environmental exposure influences disease-causing biomarkers and in turn increases disease risk.

Analysis of Ti- and Pb-based particles in the aqueous environment of Melbourne (Australia) via single particle ICP-MS.

The analysis of natural and anthropogenic nanomaterials (NMs) in the environment is challenging and requires methods capable to identify and characterise structures on the nanoscale regarding particle number concentrations (PNCs), elemental composition, size, and mass distributions. In this study, we employed single particle inductively coupled plasma-mass spectrometry (SP ICP-MS) to investigate the occurrence of NMs in the Melbourne area (Australia) across 63 locations. Poisson statistics were used to discriminate between signals from nanoparticulate matter and ionic background. TiO2-based NMs were frequently detected and corresponding NM signals were calibated with an automated data processing platform. Additionally, a method utilising a larger mass bandpass was developed to screen for particulate high-mass elements. This procedure identified Pb-based NMs in various samples. The effects of different environmental matrices consisting of fresh, brackish, or seawater were mitigated with an aerosol dilution method reducing the introduction of salt into the plasma and avoiding signal drift. Signals from TiO2- and Pb-based NMs were counted, integrated, and subsequently calibrated to determine PNCs as well as mass and size distributions. PNCs, mean sizes, particulate masses, and ionic background levels were compared across different locations and environments.

Improvement of glycemic indices by a hypocaloric legume-based DASH diet in adults with type 2 diabetes: a randomized controlled trial.

PURPOSE: The current study aimed to investigate the effects of legumes inclusion in the hypocaloric dietary approaches to stop hypertension (DASH) diet on fasting plasma glucose (FPG) and cardiometabolic risk factors in overweight and obese patients with type 2 diabetes over 16 weeks. Also, the modulatory effects of rs7903146 variant in the transcription factor 7 like 2 (TCF7L2) gene that is associated with the risk of diabetes, were assessed on these cardiometabolic risk factors. METHODS: This study was a randomized controlled trial. Three-hundred participants, aged 30-65 years, whose TCF7L2 rs7903146 genotype was determined, were studied. The participants were randomly assigned to receive either the hypocaloric DASH diet or a hypocaloric legume-based DASH diet. The primary outcome was the difference in FPG change from baseline until the 16-week follow-up between the two dietary interventions. The secondary outcomes were differences in insulin resistance and lipid profile changes between the dietary intervention diets. RESULTS: A reduction in FPG, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) was observed at week 16 in both hypocaloric dietary interventions. Compared to the DASH diet, the legume-based DASH diet decreased the FPG and HOMA-IR. There is no interaction between rs7903146 and intervention diets on glycemic parameters. CONCLUSION: The DASH diet, enrich in legumes, could improve the glycemic parameters in participants with type 2 diabetes, regardless of having rs7903146 risk or non-risk allele. REGISTRATION NUMBER OF CLINICAL TRIAL: Iranian Registry of Clinical Trials (IRCT) (code: IRCT20090203001640N17).

Transmission Route Used By Parasitic Lasidium Larvae of The Freshwater Mussel Anodontites Trapesialis on Guppies Poecilia Reticulata During Short Cohabitation.

We describe for the first time the transmission route employed by the parasitic larvae of the freshwater mussel Anodontites trapesialis (Lamarck, 1819) during cohabitation on the guppy Poecilia reticulata Peter, 1859. The freshwater mussel and fish-host were employed as a model system to investigate the infection and parasite establishment. Laboratory experiments included video recording and histopathological analysis of the infection. In vivo video observations demonstrated that lasidium larvae could be transmitted to guppies during direct contact. A series of histology samples and photography suggest that this larva attaches and colonizes possibly on-site on the outer surface of the fish, causing cellular inflammation in the epidermis layer with cellular hyperplasia in the zone of parasite attachment. An evident hyaline layer, cellular hypertrophy, and a large number of undifferentiated proliferating cells were observed. Hemorrhagic tissue and swelling were observed in the epidermis and dermic zone. The total number of larvae per male and female guppy was 525 ± 86 and 494 ± 167, respectively. No parasitic preference was detected for male versus female parasitized fish.

Successional syndromes of saplings in tropical secondary forests emerge from environment-dependent trait-demography relationships.

Identifying generalisable processes that underpin population dynamics is crucial for understanding successional patterns. While longitudinal or chronosequence data are powerful tools for doing so, the traditional focus on community-level shifts in taxonomic and functional composition rather than species-level trait-demography relationships has made generalisation difficult. Using joint species distribution models, we demonstrate how three traits-photosynthetic rate, adult stature, and seed mass-moderate recruitment and sapling mortality rates of 46 woody species during secondary succession. We show that the pioneer syndrome emerges from higher photosynthetic rates, shorter adult statures and lighter seeds that facilitate exploitation of light in younger secondary forests, while 'long-lived pioneer' and 'late successional' syndromes are associated with trait values that enable species to persist in the understory or reach the upper canopy in older secondary forests. Our study highlights the context dependency of trait-demography relationships, which drive successional shifts in sapling's species composition in secondary forests.

Gene and environmental interactions according to the components of lifestyle modifications in hypertension guidelines.

Risk factors for hypertension consist of lifestyle and genetic factors. Family history and twin studies have yielded heritability estimates of BP in the range of 34-67%. The most recent paper of BP GWAS has explained about 20% of the population variation of BP. An overestimation of heritability may have occurred in twin studies due to violations of shared environment assumptions, poor phenotyping practices in control cohorts, failure to account for epistasis, gene-gene and gene-environment interactions, and other non-genetic sources of phenotype modulation that are suspected to lead to underestimations of heritability in GWAS. The recommendations of hypertension guidelines in major countries consist of the following elements: weight reduction, a healthy diet, dietary sodium reduction, increasing physical activity, quitting smoking, and moderate alcohol consumption. The hypertension guidelines are mostly the same for each country or region, beyond race and culture. In this review, we summarize gene-environmental interactions associated with hypertension by describing lifestyle modifications according to the hypertension guidelines. In the era of precision medicine, clinicians who are responsible for hypertension management should consider the gene-environment interactions along with the appropriate lifestyle components toward the prevention and treatment of hypertension. We briefly reviewed the interaction of genetic and environmental factors along the constituent elements of hypertension guidelines, but a sufficient amount of evidence has not yet accumulated, and the results of genetic factors often differed in each study.

Type A monoamine oxidase and serotonin are coordinately involved in depressive disorders: from neurotransmitter imbalance to impaired neurogenesis.

Type A monoamine oxidase (MAOA) catabolizes monoamine transmitters, serotonin, norepinephrine and dopamine, and plays a major role in the onset, progression and therapy of neuropsychiatric disorders. In depressive disorders, increase in MAOA expression and decrease in brain levels of serotonin and norepinephrine are proposed as the major pathogenic factors. The functional polymorphism of MAOA gene and genes in serotonin signal pathway are associated with depression. This review presents recent advance in studies on the role of MAOA in major depressive disorder and related emotional disorders. MAOA and serotonin regulate the prenatal development and postnatal maintenance of brain architecture and neurocircuit, as shown by MAOA-deficient humans and MAO knockout animal models. Impaired neurogenesis in the mature hippocampus has been proposed as "adult neurogenesis" hypothesis of depression. MAOA modulates the sensitivity to stress in the stages of brain development and maturation, and the interaction of gene-environmental factors in the early stage regulates the onset of depressive behaviors in adulthood. Vice versa environmental factors affect MAOA expression by epigenetic regulation. MAO inhibitors not only restore compromised neurotransmitters, but also protect neurons from cell death in depression through induction of anti-apoptotic Bcl-2 and prosurvival neurotrophic factors, especially brain-derived neurotrophic factor, the deficiency of which is detected in depression. This review discusses novel role of MAOA and serotonin in the pathogenesis and therapy of depressive disorders.

Testing for gene-environment interaction under exposure misspecification.

Complex interplay between genetic and environmental factors characterizes the etiology of many diseases. Modeling gene-environment (GxE) interactions is often challenged by the unknown functional form of the environment term in the true data-generating mechanism. We study the impact of misspecification of the environmental exposure effect on inference for the GxE interaction term in linear and logistic regression models. We first examine the asymptotic bias of the GxE interaction regression coefficient, allowing for confounders as well as arbitrary misspecification of the exposure and confounder effects. For linear regression, we show that under gene-environment independence and some confounder-dependent conditions, when the environment effect is misspecified, the regression coefficient of the GxE interaction can be unbiased. However, inference on the GxE interaction is still often incorrect. In logistic regression, we show that the regression coefficient is generally biased if the genetic factor is associated with the outcome directly or indirectly. Further, we show that the standard robust sandwich variance estimator for the GxE interaction does not perform well in practical GxE studies, and we provide an alternative testing procedure that has better finite sample properties.

Interaction of heat shock protein 70 (HSP70) polymorphisms and occupational hazards increases the risk of hypertension in coke oven workers.

OBJECTIVES: The interaction between genetic, epigenetic inheritance and environmental factors determines susceptibility to hypertension. Previous epidemiology studies have shown that coke oven workers who are frequently exposed to various occupational hazards have remarkable increase in the risk for hypertension. Among many genetic variants identified in hypertension, heat shock protein 70 (HSP70) was found to play important roles in the pathogenesis of hypertension and associated diseases. We therefore explore the possible role of HSP70 polymorphisms and their interaction with occupational environment in hypertension risk. METHODS: We carried out a case-control study among 367 coke oven workers in northwest China, focused on three common HSP70 polymorphisms (HSP70-1 G190C, HSP70-2 A1267G and HSP70-hom T2437C), and evaluated the association of HSP70 gene polymorphisms with work sites for high risk of hypertension. RESULTS: The results indicated that HSP70-1 GC and CC genotype had 2.73-fold and 4.26-fold increased relative risk (95% CI 1.33 to 5.55 and 1.17 to 15.53), respectively, comparing with HSP70-1 GG genotype. HSP70-2 AG and GG conferred a 47% and 36% reduced risk (95% CI 0.23 to 0.99 and 0.14 to 0.92) comparing with HSP70-2 AA genotype. Further analysis of the interaction of HSP70 polymorphisms with occupational environment indicated a strong positive interaction between HSP70 genotype (HSP70-1 GC+CC, HSP70-2 AA and HSP70-hom TC+CC) and oven top workplace. CONCLUSIONS: Collectively, these data indicate that HSP70 polymorphisms interact with occupational hazards might increase the risk of hypertension in coke oven workers.

Detecting population-environmental interactions with mismatched time series data.

Time series analysis is an essential method for decomposing the influences of density and exogenous factors such as weather and climate on population regulation. However, there has been little work focused on understanding how well commonly collected data can reconstruct the effects of environmental factors on population dynamics. We show that, analogous to similar scale issues in spatial data analysis, coarsely sampled temporal data can fail to detect covariate effects when interactions occur on timescales that are fast relative to the survey period. We propose a method for modeling mismatched time series data that couples high-resolution environmental data to low-resolution abundance data. We illustrate our approach with simulations and by applying it to Florida's southern Snail kite population. Our simulation results show that our method can reliably detect linear environmental effects and that detecting nonlinear effects requires high-resolution covariate data even when the population turnover rate is slow. In the Snail kite analysis, our approach performed among the best in a suite of previously used environmental covariates explaining Snail kite dynamics and was able to detect a potential phenological shift in the environmental dependence of Snail kites. Our work provides a statistical framework for reliably detecting population-environment interactions from coarsely surveyed time series. An important implication of this work is that the low predictability of animal population growth by weather variables found in previous studies may be due, in part, to how these data are utilized as covariates.

Susceptibility to human cancer: From the perspective of a pathologist.

The etiologies of human cancer can only be discerned when the genetic clustering of cancer occurs within a family or when cancer occurs endemically in a particular environment. The possible approaches to solving the nature/nurture problem, especially for human carcinogenesis, posit a fascinating challenge for pathologists. This perspective review presents some examples of how clues to human cancer etiologies and/or susceptibilities reside in the realm of pathology practice. These examples using various omics techniques including adductomics, which I would like to highlight in this article, show that the currently available concepts and methods in human pathology can open a path toward the brave new world of a post-genomic era of medicine for young pathologists, whether their original intention was toward the pursuit of diagnostic or investigative knowledge.

Transcriptome-wide characterization of candidate genes for improving the water use efficiency of energy crops grown on semiarid land.

Understanding the genetic basis of water use efficiency (WUE) and its roles in plant adaptation to a drought environment is essential for the production of second-generation energy crops in water-deficit marginal land. In this study, RNA-Seq and WUE measurements were performed for 78 individuals of Miscanthus lutarioriparius grown in two common gardens, one located in warm and wet Central China near the native habitats of the species and the other located in the semiarid Loess Plateau, the domestication site of the energy crop. The field measurements showed that WUE of M. lutarioriparius in the semiarid location was significantly higher than that in the wet location. A matrix correlation analysis was conducted between gene expression levels and WUE to identify candidate genes involved in the improvement of WUE from the native to the domestication site. A total of 48 candidate genes were identified and assigned to functional categories, including photosynthesis, stomatal regulation, protein metabolism, and abiotic stress responses. Of these genes, nearly 73% were up-regulated in the semiarid site. It was also found that the relatively high expression variation of the WUE-related genes was affected to a larger extent by environment than by genetic variation. The study demonstrates that transcriptome-wide correlation between physiological phenotypes and expression levels offers an effective means for identifying candidate genes involved in the adaptation to environmental changes.

Does Environmental Knowledge Inhibit Hominin Dispersal?

We investigated the relationship between the dispersal potential of a hominin population, its local-scale foraging strategies, and the characteristics of the resource environment using an agent-based modeling approach. In previous work we demonstrated that natural selection can favor a relatively low capacity for assessing and predicting the quality of the resource environment, especially when the distribution of resources is highly clustered. That work also suggested that the more knowledge foraging populations had about their environment, the less likely they were to abandon the landscape they know and disperse into novel territory. The present study gives agents new individual and social strategies for learning about their environment. For both individual and social learning, natural selection favors decreased levels of environmental knowledge, particularly in low-heterogeneity environments. Social acquisition of detailed environmental knowledge results in crowding of agents, which reduces available reproductive space and relative fitness. Agents with less environmental knowledge move away from resource clusters and into areas with more space available for reproduction. These results suggest that, rather than being a requirement for successful dispersal, environmental knowledge strengthens the ties to particular locations and significantly reduces the dispersal potential as a result. The evolved level of environmental knowledge in a population depends on the characteristics of the resource environment and affects the dispersal capacity of the population.

Associations between CLCNKA_B tag SNPs with essential hypertension and interactions between genetic and environmental factors in an island population in China.

OBJECTIVE: Essential hypertension (EH) is known as the result from the interaction of environmental and genetic factors. We selected tag SNPs of CLCNKA_B genes as gene markers, to elucidate the relationship between CLCNKA_B and EH, and to determine the possible interaction among tag SNPs and dietary factors in island of China. METHODS: A case-control study was conducted in Changshan islands of China, blood samples of 806 participants were genotyped, and the general characteristics and dietary habits of them were collected. Unconditional logistic regression (ULR) was used to assess the effects of CLCNKA_B tag SNPs and dietary factors on EH. Generalized multifactor dimensionality reduction (GMDR) was used to test gene-environment interaction for EH risk. RESULTS: Four SNPs were identified as the tag SNPs of CLCNKA_B. Recessive model for rs5253 and rs2275166 were marginal associated with the decrease risk of EH (OR = 0.36, 95% CI = 0.12-1.07 for rs5253; OR = 0.40, 95% CI = 0.16-1.05 for rs2275166). In GMDR, the five-factor interaction model of rs1010069, salt, marine products, meat and edible oil consumption was the best model, with a maximum CVC of 10/10 and a TBA of 0.638 (p = 0.001). In ULR, compared with subjects carried wild genotypes and null dietary risk factor, those with three or more dietary risk factors and mutation genotypes had 5.90-fold EH risk (95% CI:2.24-15.53). CONCLUSION: Though the single loci of tag SNPs of CLCNKA_B are not enough to significantly increase the EH susceptibility, the combination of CLCNKA tag SNP, salt, marine products, meat and edible oil consumption is associated with elevated risk.

Genetics of anxiety disorders: Genetic epidemiological and molecular studies in humans.

This review provides a broad overview of the state of research in the genetics of anxiety disorders (AD). Genetic epidemiological studies report a moderate level of familial aggregation (odds ratio: 4-6) and heritability estimates are about 30-50%. Twin studies suggest that the genetic architecture of AD is not isomorphic with their classifications, sharing risk factors with each other. So far, linkage and association studies of AD have produced inconclusive results. Genome-wide association studies of AD can provide an unbiased survey of common genetic variations across the entire genome. Given the shared causes of AD that transcend our current diagnostic classifications, clustering anxiety phenotypes into broader groups may be a powerful approach to identifying susceptibility locus for AD. Using such a shared genetic risk factor, meta-analyses of genome-wide association studies of AD conducted by large consortia are needed. Environmental factors also make a substantial contribution to the cause of AD. Although candidate gene studies of gene by environmental (G × E) interaction have appeared recently, no genome-wide search for G × E interactions have been performed. Epigenetic modification of DNA appears to have important effects on gene expression mediating environmental influences on disease risk. Given that G × E can be linked to an epigenetic modification, a combination analysis of genome-wide G × E interaction and methylation could be an alternative method to find risk variants for AD. This genetic research will enable us to utilize more effective strategies for the prevention and treatment of AD in the near future.