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  1. Dimitrakopoulou VI, Travis RC, Shui IM, Mondul A, Albanes D, Virtamo J, et al.
    Am J Epidemiol, 2017 Mar 15;185(6):452-464.
    PMID: 28399564 DOI: 10.1093/aje/kww143
    Genome-wide association studies (GWAS) have identified over 100 single nucleotide polymorphisms (SNPs) associated with prostate cancer. However, information on the mechanistic basis for some associations is limited. Recent research has been directed towards the potential association of vitamin D concentrations and prostate cancer, but little is known about whether the aforementioned genetic associations are modified by vitamin D. We investigated the associations of 46 GWAS-identified SNPs, circulating concentrations of 25-hydroxyvitamin D (25(OH)D), and prostate cancer (3,811 cases, 511 of whom died from the disease, compared with 2,980 controls-from 5 cohort studies that recruited participants over several periods beginning in the 1980s). We used logistic regression models with data from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) to evaluate interactions on the multiplicative and additive scales. After allowing for multiple testing, none of the SNPs examined was significantly associated with 25(OH)D concentration, and the SNP-prostate cancer associations did not differ by these concentrations. A statistically significant interaction was observed for each of 2 SNPs in the 8q24 region (rs620861 and rs16902094), 25(OH)D concentration, and fatal prostate cancer on both multiplicative and additive scales (P ≤ 0.001). We did not find strong evidence that associations between GWAS-identified SNPs and prostate cancer are modified by circulating concentrations of 25(OH)D. The intriguing interactions between rs620861 and rs16902094, 25(OH)D concentration, and fatal prostate cancer warrant replication.
    Matched MeSH terms: Gene-Environment Interaction*
  2. Agha S, Mekkawy W, Ibanez-Escriche N, Lind CE, Kumar J, Mandal A, et al.
    Anim. Genet., 2018 Oct;49(5):421-427.
    PMID: 30058152 DOI: 10.1111/age.12680
    Robustness has become a highly desirable breeding goal in the globalized agricultural market. Both genotype-by-environment interaction (G × E) and micro-environmental sensitivity are important robustness components of aquaculture production, in which breeding stock is often disseminated to different environments. The objectives of this study were (i) to quantify the degree of G × E by assessing the growth performance of Genetically Improved Farmed Tilapia (GIFT) across three countries (Malaysia, India and China) and (ii) to quantify the genetic heterogeneity of environmental variance for body weight at harvest (BW) in GIFT as a measure of micro-environmental sensitivity. Selection for BW was carried out for 13 generations in Malaysia. Subsets of 60 full-sib families from Malaysia were sent to China and India after five and nine generations respectively. First, a multi-trait animal model was used to analyse the BW in different countries as different traits. The results indicate a strong G × E. Second, a genetically structured environmental variance model, implemented using Bayesian inference, was used to analyse micro-environmental sensitivity of BW in each country. The analysis revealed the presence of genetic heterogeneity of both BW and its environmental variance in all environments. The presence of genetic variation in residual variance of BW implies that the residual variance can be modified by selection. Incorporating both G × E and micro-environmental sensitivity information may help in selecting robust genotypes with high performance across environments and resilience to environmental fluctuations.
    Matched MeSH terms: Gene-Environment Interaction*
  3. Too CL, Muhamad NA, Ilar A, Padyukov L, Alfredsson L, Klareskog L, et al.
    Ann Rheum Dis, 2016 06;75(6):997-1002.
    PMID: 26681695 DOI: 10.1136/annrheumdis-2015-208278
    OBJECTIVES: Lung exposures including cigarette smoking and silica exposure are associated with the risk of rheumatoid arthritis (RA). We investigated the association between textile dust exposure and the risk of RA in the Malaysian population, with a focus on women who rarely smoke.

    METHODS: Data from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis population-based case-control study involving 910 female early RA cases and 910 female age-matched controls were analysed. Self-reported information on ever/never occupationally exposed to textile dust was used to estimate the risk of developing anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA. Interaction between textile dust and the human leucocyte antigen DR β-1 (HLA-DRB1) shared epitope (SE) was evaluated by calculating the attributable proportion due to interaction (AP), with 95% CI.

    RESULTS: Occupational exposure to textile dust was significantly associated with an increased risk of developing RA in the Malaysian female population (OR 2.8, 95% CI 1.6 to 5.2). The association between occupational exposure to textile dust and risk of RA was uniformly observed for the ACPA-positive RA (OR 2.5, 95% CI 1.3 to 4.8) and ACPA-negative RA (OR 3.5, 95% CI 1.7 to 7.0) subsets, respectively. We observed a significant interaction between exposure to occupational textile dust and HLA-DRB1 SE alleles regarding the risk of ACPA-positive RA (OR for double exposed: 39.1, 95% CI 5.1 to 297.5; AP: 0.8, 95% CI 0.5 to 1.2).

    CONCLUSIONS: This is the first study demonstrating that textile dust exposure is associated with an increased risk for RA. In addition, a gene-environment interaction between HLA-DRB1 SE and textile dust exposure provides a high risk for ACPA-positive RA.
    Matched MeSH terms: Gene-Environment Interaction
  4. Meng W, Zhu Z, Jiang X, Too CL, Uebe S, Jagodic M, et al.
    Arthritis Res Ther, 2017 03 29;19(1):71.
    PMID: 28356135 DOI: 10.1186/s13075-017-1276-2
    BACKGROUND: Multiple factors, including interactions between genetic and environmental risks, are important in susceptibility to rheumatoid arthritis (RA). However, the underlying mechanism is not fully understood. This study was undertaken to evaluate whether DNA methylation can mediate the interaction between genotype and smoking in the development of anti-citrullinated peptide antibody (ACPA)-positive RA.

    METHODS: We investigated the gene-smoking interactions in DNA methylation using 393 individuals from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA). The interaction between rs6933349 and smoking in the risk of developing ACPA-positive RA was further evaluated in a larger portion of the EIRA (1119 controls and 944 ACPA-positive patients with RA), and in the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) (1556 controls and 792 ACPA-positive patients with RA). Finally, mediation analysis was performed to investigate whether DNA methylation of cg21325723 mediates this gene-environment interaction on the risk of developing of ACPA-positive RA.

    RESULTS: We identified and replicated one significant gene-environment interaction between rs6933349 and smoking in DNA methylation of cg21325723. This gene-smoking interaction is a novel interaction in the risk of developing ACPA-positive in both Caucasian (multiplicative P value = 0.056; additive P value = 0.016) and Asian populations (multiplicative P value = 0.035; additive P value = 0.00027), and it is mediated through DNA methylation of cg21325723.

    CONCLUSIONS: We showed that DNA methylation of cg21325723 can mediate the gene-environment interaction between rs6933349 and smoking, impacting the risk of developing ACPA-positive RA, thus being a potential regulator that integrates both internal genetic and external environmental risk factors.
    Matched MeSH terms: Gene-Environment Interaction*
  5. Ahmed F, Rafii MY, Ismail MR, Juraimi AS, Rahim HA, Asfaliza R, et al.
    Biomed Res Int, 2013;2013:963525.
    PMID: 23484164 DOI: 10.1155/2013/963525
    Submergence or flood is one of the major harmful abiotic stresses in the low-lying countries and crop losses due to waterlogging are considerably high. Plant breeding techniques, conventional or genetic engineering, might be an effective and economic way of developing crops to grow successfully in waterlogged condition. Marker assisted selection (MAS) is a new and more effective approach which can identify genomic regions of crops under stress, which could not be done previously. The discovery of comprehensive molecular linkage maps enables us to do the pyramiding of desirable traits to improve in submergence tolerance through MAS. However, because of genetic and environmental interaction, too many genes encoding a trait, and using undesirable populations the mapping of QTL was hampered to ensure proper growth and yield under waterlogged conditions Steady advances in the field of genomics and proteomics over the years will be helpful to increase the breeding programs which will help to accomplish a significant progress in the field crop variety development and also improvement in near future. Waterlogging response of soybean and major cereal crops, as rice, wheat, barley, and maize and discovery of QTL related with tolerance of waterlogging, development of resistant variety, and, in addition, future prospects have also been discussed.
    Matched MeSH terms: Gene-Environment Interaction*
  6. Peyrot WJ, Van der Auwera S, Milaneschi Y, Dolan CV, Madden PAF, Sullivan PF, et al.
    Biol Psychiatry, 2018 Jul 15;84(2):138-147.
    PMID: 29129318 DOI: 10.1016/j.biopsych.2017.09.009
    BACKGROUND: The heterogeneity of genetic effects on major depressive disorder (MDD) may be partly attributable to moderation of genetic effects by environment, such as exposure to childhood trauma (CT). Indeed, previous findings in two independent cohorts showed evidence for interaction between polygenic risk scores (PRSs) and CT, albeit in opposing directions. This study aims to meta-analyze MDD-PRS × CT interaction results across these two and other cohorts, while applying more accurate PRSs based on a larger discovery sample.

    METHODS: Data were combined from 3024 MDD cases and 2741 control subjects from nine cohorts contributing to the MDD Working Group of the Psychiatric Genomics Consortium. MDD-PRS were based on a discovery sample of ∼110,000 independent individuals. CT was assessed as exposure to sexual or physical abuse during childhood. In a subset of 1957 cases and 2002 control subjects, a more detailed five-domain measure additionally included emotional abuse, physical neglect, and emotional neglect.

    RESULTS: MDD was associated with the MDD-PRS (odds ratio [OR] = 1.24, p = 3.6 × 10-5, R2 = 1.18%) and with CT (OR = 2.63, p = 3.5 × 10-18 and OR = 2.62, p = 1.4 ×10-5 for the two- and five-domain measures, respectively). No interaction was found between MDD-PRS and the two-domain and five-domain CT measure (OR = 1.00, p = .89 and OR = 1.05, p = .66).

    CONCLUSIONS: No meta-analytic evidence for interaction between MDD-PRS and CT was found. This suggests that the previously reported interaction effects, although both statistically significant, can best be interpreted as chance findings. Further research is required, but this study suggests that the genetic heterogeneity of MDD is not attributable to genome-wide moderation of genetic effects by CT.

    Matched MeSH terms: Gene-Environment Interaction
  7. Michal Christina Steven
    Borneo Epidemiology Journal, 2020;1(2):104-115.
    MyJurnal
    Introduction:Plasmodium knowlesi(P.knowlesi) is a zoonotic malaria parasite, transmitted between non-factors” or “individual factors” or “ecological factors” and “P.knowlesi” and “human” including human primate hosts by the Anopheles (An.) mosquitos, and causing spill-over infections in humans where the parasite, vector, host, and human converge
    Methods:The search was done electronically toexplore for appropriate papers viaPubMed, and Science Direct for articles published up to March 2020, containing the words “factors associated” or “environmental synonyms and Medical Subject Heading (MeSH) terms. A total of 27 articles from PubMed Databases and 18 articles from Science Direct were selected to be assessed for eligibility. Out of it, a total of 13 articles were selected to be analysed.
    Results:Host factors such as sex and age, as well as occupation as individual factors, while environmental factors such as rainfall and geographic elevation have some association with P.knowlesiinfection in humans. This zoonotic malaria poses unique challenges that will need to be addressed if all forms of malaria are to be eliminated based on the sustainable development goal (SDG)
    Conclusion:This article highlights the importance of disease ecologies such as climate and landscape and human-environment interactions such as the land use patterns, such as agriculture or infrastructure activities) to reduce the further increase of cases and mortality globally due to P.knowlesiinfection. This review focuses mainly on the host and environmental factors that influence P.knowlesiMalaria Infection in Humans
    Matched MeSH terms: Gene-Environment Interaction
  8. Ahmad N, Shah SA, Abdul Gafor AH, Abdul Murad NA, Kamaruddin MA, Abd Jalal N, et al.
    Diabet Med, 2020 11;37(11):1890-1901.
    PMID: 32012348 DOI: 10.1111/dme.14257
    AIM: To examine the possible gene-environment interactions between 32 single nucleotide polymorphisms and environmental factors that could modify the probability of chronic kidney disease.

    METHODS: A case-control study was conducted involving 600 people with type 2 diabetes (300 chronic kidney disease cases, 300 controls) who participated in The Malaysian Cohort project. Retrospective subanalysis was performed on the chronic kidney disease cases to assess chronic kidney disease progression from the recruitment phase. We genotyped 32 single nucleotide polymorphisms using mass spectrometry. The probability of chronic kidney disease and predicted rate of newly detected chronic kidney disease progression were estimated from the significant gene-environment interaction analyses.

    RESULTS: Four single nucleotide polymorphisms (eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228) and five environmental factors (age, sex, smoking, waist circumference and HDL) were significantly associated with chronic kidney disease. Gene-environment interaction analyses revealed significant probabilities of chronic kidney disease for sex (PPARGC1A rs8192678), smoking (eNOS rs2070744, PPARGC1A rs8192678 and KCNQ1 rs2237895), waist circumference (eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228) and HDL (eNOS rs2070744 and PPARGC1A rs8192678). Subanalysis indicated that the rate of newly detected chronic kidney disease progression was 133 cases per 1000 person-years (95% CI: 115, 153), with a mean follow-up period of 4.78 (SD 0.73) years. There was a significant predicted rate of newly detected chronic kidney disease progression in gene-environment interactions between KCNQ1 rs2283228 and two environmental factors (sex and BMI).

    CONCLUSIONS: Our findings suggest that the gene-environment interactions of eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228 with specific environmental factors could modify the probability for chronic kidney disease.

    Matched MeSH terms: Gene-Environment Interaction
  9. Williams R, Periasamy M
    Endocrinol Metab (Seoul), 2020 12;35(4):681-695.
    PMID: 33397033 DOI: 10.3803/EnM.2020.772
    Obesity-associated metabolic illnesses are increasing at an alarming rate in Asian countries. A common feature observed in the Asian population is a higher incidence of abdominal obesity-the "skinny-fat" Asian syndrome. In this review, we critically evaluate the relative roles of genetics and environmental factors on fat distribution in Asian populations. While there is an upward trend in obesity among most Asian countries, it appears particularly conspicuous in Malaysia. We propose a novel theory, the Malaysian gene-environment multiplier hypothesis, which explains how ancestral variations in feast-and-famine cycles contribute to inherited genetic predispositions that, when acted on by modern-day stressors-most notably, urbanization, westernization, lifestyle changes, dietary transitions, cultural pressures, and stress-contribute to increased visceral adiposity in Asian populations. At present, the major determinants contributing to visceral adiposity in Asians are far from conclusive, but we seek to highlight critical areas for further research.
    Matched MeSH terms: Gene-Environment Interaction*
  10. Nguyen NH, Hamzah A, Thoa NP
    Front Genet, 2017;8:82.
    PMID: 28659970 DOI: 10.3389/fgene.2017.00082
    The extent to which genetic gain achieved from selection programs under strictly controlled environments in the nucleus that can be expressed in commercial production systems is not well-documented in aquaculture species. The main aim of this paper was to assess the effects of genotype by environment interaction on genetic response and genetic parameters for four body traits (harvest weight, standard length, body depth, body width) and survival in Red tilapia (Oreochromis spp.). The growth and survival data were recorded on 19,916 individual fish from a pedigreed population undergoing three generations of selection for increased harvest weight in earthen ponds from 2010 to 2012 at the Aquaculture Extension Center, Department of Fisheries, Jitra in Kedah, Malaysia. The pedigree comprised a total of 224 sires and 262 dams, tracing back to the base population in 2009. A multivariate animal model was used to measure genetic response and estimate variance and covariance components. When the homologous body traits in freshwater pond and cage were treated as genetically distinct traits, the genetic correlations between the two environments were high (0.85-0.90) for harvest weight and square root of harvest weight but the estimates were of lower magnitudes for length, width and depth (0.63-0.79). The heritabilities estimated for the five traits studied differed between pond (0.02 to 0.22) and cage (0.07 to 0.68). The common full-sib effects were large, ranging from 0.23 to 0.59 in pond and 0.11 to 0.31 in cage across all traits. The direct and correlated responses for four body traits were generally greater in pond than in cage environments (0.011-1.561 vs. -0.033-0.567 genetic standard deviation units, respectively). Selection for increased harvest body weight resulted in positive genetic changes in survival rate in both pond and cage culture. In conclusion, the reduced selection response and the magnitude of the genetic parameter estimates in the production environment (i.e., cage) relative to those achieved in the nucleus (pond) were a result of the genotype by environment interaction and this effect should be taken into consideration in the future breeding program for Red tilapia.
    Matched MeSH terms: Gene-Environment Interaction
  11. Romli MH, Mackenzie L, Lovarini M, Clemson L, Tan MP
    Front Public Health, 2020;8:612599.
    PMID: 33511098 DOI: 10.3389/fpubh.2020.612599
    Background: Fear of falling (FoF) is a common issue among older people, impacting on psychological health, functional performance and mortality. Many factors associated with fear of falling have been investigated but little is known about the role of home hazards. Home hazards can be due to unsafe environmental and functional features. This study is aims to evaluate the association between home hazards with fear of falling among community-dwelling individuals aged 55 years and over. Methods: Baseline data with 1,489 older individuals from the Malaysian Elders Longitudinal Research (MELoR) study were analyzed. Home visits for interview and observations in the home were conducted with the participants. FoF was established with a single-item question and home hazards with the Home Falls and Accidents Screening Tool (HOME FAST). Results: The majority (76.4%) of older participants experienced FoF. The history of falls was not associated with FoF (p = 0.868), but FoF was associated with participants limiting their daily activities (p < 0.001). Home hazards were less likely (p = 0.023) and functional issues were more likely (p < 0.001) to be associated with a high degree of FoF. However, both home hazards domains were not associated with activity restriction due to FoF. Conclusions: Education about home hazards from the perspective of person-environment interaction may encourage home hazards management and reduce FoF which should be evaluated in future studies.
    Matched MeSH terms: Gene-Environment Interaction
  12. Rafii MY, Jalani BS, Rajanaidu N, Kushairi A, Puteh A, Latif MA
    Genet. Mol. Res., 2012;11(4):3629-41.
    PMID: 23096688 DOI: 10.4238/2012.October.4.10
    We evaluated 38 dura x pisifera (DP) oil palm progenies in four locations in Malaysia for genotype by environment interaction and genotypic stability studies. The DP progenies derived from crosses between pisifera palms of AVROS, Serdang S27B, Serdang 29/36, and Lever Cameroon were chosen to be the males' parent and Deli dura palms designated as females' parent. All the locations differed in terms of soil physical and chemical properties, and the soil types ranged from coastal clay to inland soils. The genotype by environment interaction and stability of the individual genotypes were analyzed for oil yield trait using several stability techniques. A genotype by environment interaction was detected for oil yield and it had a larger variance component than genotypic variance (σ(2)(gl)/σ(2)(g) = 139.7%). Genotype by environment interaction of oil yield was largely explained by a non-linear relationship between genotypic and environmental values. Overall assessment of individual genotypic stability showed that seven genotypes were highly stable and had consistent performance over the environments for the oil yield trait [total individual genotype stability scored more than 10 and mean oil yielded above the average of the environment (genotype means are more than 34.37 kg·palm(-1)·year(-1))]. These genotypes will be useful for oil palm breeding and tissue culture programs for developing high oil yielding planting materials with stable performance.
    Matched MeSH terms: Gene-Environment Interaction
  13. Shafii NZ, Saudi ASM, Pang JC, Abu IF, Sapawe N, Kamarudin MKA, et al.
    Heliyon, 2019 Oct;5(10):e02534.
    PMID: 31667387 DOI: 10.1016/j.heliyon.2019.e02534
    There has been a growing concern on the rising of environmental issues in Malaysia over the last decade. Many environmental studies conducted in this country began to utilise the chemometrics techniques to overcome the limitation in the environmental monitoring studies. Chemometrics becomes an important tool in environmental fields to evaluate the relationship of various environmental variables particularly in a large and complex database. The review aimed to analyse and summarize the current evidences and limitations on the application of chemometrics techniques in the environmental studies in Malaysia. The study performed a comprehensive review of relevant scientific journals concerning on the major environmental issues in the country, published between 2013 and 2017. A total of 29 papers which focused on the environmental issues were reviewed. Available evidences suggested that chemometrics techniques have a greater accuracy, flexibility and efficiency to be applied in environmental modelling. It also reported that chemometrics techniques are more practical for cost effective and time management in sampling and monitoring purposes. However, chemometrics is relatively new in environmental field in Malaysia and various scopes need to be considered in the future as the current studies focused on very limited number of major environmental issues. Overall, chemometrics techniques have a lot of advantages in solving environmental problems. The development of chemometrics in environmental studies in the country is necessary to advance understanding, thus able to produce more significant impacts towards the effective environmental management.
    Matched MeSH terms: Gene-Environment Interaction
  14. Jamal R, Syed Zakaria SZ, Kamaruddin MA, Abd Jalal N, Ismail N, Mohd Kamil N, et al.
    Int J Epidemiol, 2015 Apr;44(2):423-31.
    PMID: 24729425 DOI: 10.1093/ije/dyu089
    The Malaysian Cohort study was initiated in 2005 by the Malaysian government. The top-down approach to this population-based cohort study ensured the allocation of sufficient funding for the project which aimed to recruit 100,000 individuals aged 35-70 years. Participants were recruited from rural and urban areas as well as from various socioeconomic groups. The main objectives of the study were to identify risk factors, to study gene-environment interaction and to discover biomarkers for the early detection of cancers and other diseases. At recruitment, a questionnaire-based interview was conducted, biophysical measurements were performed and biospecimens were collected, processed and stored. Baseline investigations included fasting blood sugar, fasting lipid profile, renal profile and full blood count. From April 2006 to the end of September 2012 we recruited a total of 106,527 participants. The baseline prevalence data showed 16.6% participants with diabetes, 46.5% with hypertension, 44.9% with hypercholesterolaemia and 17.7% with obesity. The follow-up phase commenced in June 2013. This is the most comprehensive and biggest cohort study in Malaysia, and has become a valuable resource for epidemiological and biological research. For information on collaboration and also data access, investigators can contact the project leader at (rahmanj@ppukm.ukm.edu.my).
    Study name: The Malaysian Cohort (TMC) project
    Matched MeSH terms: Gene-Environment Interaction
  15. Yap RW, Shidoji Y, Hon WM, Masaki M
    J Nutrigenet Nutrigenomics, 2011;4(6):309-21.
    PMID: 22301682 DOI: 10.1159/000334358
    The prevalence of lifestyle-related chronic diseases is increasing and gene-diet interaction studies are limited among the Malaysian population. This study was conducted to evaluate the association and interaction effects of vascular endothelial growth factor receptor-2(VEGFR2) gene polymorphisms and dietary patterns on anthropometric and biochemical risk factors of chronic diseases in 179 Chinese Malaysian adults.
    Matched MeSH terms: Gene-Environment Interaction
  16. Ellulu MS, Jalambo MO
    Kathmandu Univ Med J (KUMJ), 2018 2 16;15(57):91-93.
    PMID: 29446373
    Urbanization has provided experimental settings for testing the interactive relationship between genetic background and changes in lifestyle and dietary patterns. The concept of gene-environment interaction was described by epidemic of obesity along with urbanization. Genome-wide association has identified several genes such as melanocortin-4 receptor that associates with environmental influences of obesity. Gene environment (GxE) interaction refers to modification by an environmental factor of the effect of a genetic variant on a phenotypic trait. GxE interactions can serve to modulate the adverse effects of a risk allele, or can exacerbate the genotype-phenotype relationship and increase risk.
    Matched MeSH terms: Gene-Environment Interaction*
  17. Tan PY, Mitra SR
    Lifestyle Genom, 2020;13(2):84-98.
    PMID: 32101872 DOI: 10.1159/000505662
    BACKGROUND: Computing polygenic risk scores (PRS) to predict the degree of risk for obesity may contribute to weight management programs strategically.

    OBJECTIVES: To investigate the combined effect of FTO rs9930501, rs9930506, and rs9932754 and ADRB2 rs1042713 and rs1042714 using PRS on (1) the odds of obesity and (2) post-intervention differences in dietary, anthropometric, and cardiometabolic parameters in response to high-protein calorie-restricted, high-vitamin E, high-fiber (Hipcref) diet intervention in Malaysian adults.

    METHODS: Both a cross-sectional study (n = 178) and a randomized controlled trial (RCT) (n = 128) were conducted to test the aforementioned objectives. PRS was computed as the weighted sum of the risk alleles possessed by each individual participant. Participants were stratified into first (PRS 0-0.64), second (PRS 0.65-3.59), and third (PRS 3.60-8.18) tertiles.

    RESULTS: The third tertile of PRS was associated with significantly higher odds of obesity: 2.29 (95% CI = 1.11-4.72, adjusted p = 0.025) compared to the first tertile. Indians (3.9 ± 0.3) had significantly higher PRS compared to Chinese (2.1 ± 0.4) (p = 0.010). In the RCT, a greater reduction in high-sensitivity C-reactive protein (hsCRP) levels was found in second and third tertiles after Hipcref diet intervention compared to the control diet (p interaction = 0.048).

    CONCLUSION: Higher PRS was significantly associated with increased odds of obesity. Individuals with higher PRS had a significantly greater reduction in hsCRP levels after Hipcref diet compared to the control diet.

    Matched MeSH terms: Gene-Environment Interaction
  18. Buji RI, Abdul Murad NA, Chan LF, Maniam T, Mohd Shahrir MS, Rozita M, et al.
    Lupus, 2018 Apr;27(5):744-752.
    PMID: 29161964 DOI: 10.1177/0961203317742711
    Background Systemic lupus erythematosus (SLE) patients are a high-risk population for suicide. Glutamatergic neurosystem genes have been implicated in the neurobiology of depression in SLE and suicidal behaviour in general. However, the role of glutamate receptor gene polymorphisms in suicidal behaviour among SLE patients remains unclear in the context of established clinical and psychosocial factors. We aimed to investigate the association of NR2A gene polymorphism with suicidal ideation in SLE while accounting for the interaction between clinical and psychosocial factors. Methods A total of 130 SLE patients were assessed for mood disorders (MINI International Neuropsychiatric Interview), severity of depression (Patient Health Questionnaire-9), suicidal behaviour (Columbia-Suicide Severity Rating Scale), socio-occupational functioning (Work and Social Adjustment Scale), recent life events (Social Readjustment Rating Scale) and lupus disease activity (SELENA-SLE Disease Activity Index). Eighty-six out of the 130 study participants consented for NR2A genotyping. Results Multivariable logistic regression showed nominal significance for the interaction effect between the NR2A rs2072450 AC genotype and higher severity of socio-occupational impairment with lifetime suicidal ideation in SLE patients ( p = 0.038, odds ratio = 1.364, 95% confidence interval = 1.018-1.827). However, only the association between lifetime mood disorder and lifetime suicidal ideation remained significant after Bonferroni correction ( p gene polymorphism main and interaction effects. Clinical implications include identification and treatment of mood disorders as an early intervention for suicidal behaviour in SLE. More adequately-powered gene-environment interaction studies are required in the future to clarify the role of glutamate receptor gene polymorphisms in the risk stratification of suicidal behaviour among SLE patients.
    Study site: outpatient clinics and in-patient wards, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
    Matched MeSH terms: Gene-Environment Interaction
  19. Ugai T, Milne RL, Ito H, Aronson KJ, Bolla MK, Chan T, et al.
    Mol Genet Genomic Med, 2019 Jun;7(6):e707.
    PMID: 31066241 DOI: 10.1002/mgg3.707
    BACKGROUND: Epidemiological studies consistently indicate that alcohol consumption is an independent risk factor for female breast cancer (BC). Although the aldehyde dehydrogenase 2 (ALDH2) polymorphism (rs671: Glu>Lys) has a strong effect on acetaldehyde metabolism, the association of rs671 with BC risk and its interaction with alcohol intake have not been fully elucidated. We conducted a pooled analysis of 14 case-control studies, with individual data on Asian ancestry women participating in the Breast Cancer Association Consortium.

    METHODS: We included 12,595 invasive BC cases and 12,884 controls for the analysis of rs671 and BC risk, and 2,849 invasive BC cases and 3,680 controls for the analysis of the gene-environment interaction between rs671 and alcohol intake for BC risk. The pooled odds ratios (OR) with 95% confidence intervals (CI) associated with rs671 and its interaction with alcohol intake for BC risk were estimated using logistic regression models.

    RESULTS: The Lys/Lys genotype of rs671 was associated with increased BC risk (OR = 1.16, 95% CI 1.03-1.30, p = 0.014). According to tumor characteristics, the Lys/Lys genotype was associated with estrogen receptor (ER)-positive BC (OR = 1.19, 95% CI 1.05-1.36, p = 0.008), progesterone receptor (PR)-positive BC (OR = 1.19, 95% CI 1.03-1.36, p = 0.015), and human epidermal growth factor receptor 2 (HER2)-negative BC (OR = 1.25, 95% CI 1.05-1.48, p = 0.012). No evidence of a gene-environment interaction was observed between rs671 and alcohol intake (p = 0.537).

    CONCLUSION: This study suggests that the Lys/Lys genotype confers susceptibility to BC risk among women of Asian ancestry, particularly for ER-positive, PR-positive, and HER2-negative tumor types.

    Matched MeSH terms: Gene-Environment Interaction
  20. Peyrot WJ, Lee SH, Milaneschi Y, Abdellaoui A, Byrne EM, Esko T, et al.
    Mol Psychiatry, 2015 Jun;20(6):735-43.
    PMID: 25917368 DOI: 10.1038/mp.2015.50
    An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotropic genetic effects contribute to this association. Therefore, data were analyzed from a total of 9662 major depressive disorder (MDD) cases and 14,949 controls (with no lifetime MDD diagnosis) from the Psychiatric Genomics Consortium with additional Dutch and Estonian data. The association of EA and MDD was assessed with logistic regression in 15,138 individuals indicating a significantly negative association in our sample with an odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in EA. With data of 884,105 autosomal common single-nucleotide polymorphisms (SNPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk scores (GPRS) derived from training data for EA (independent meta-analysis on ~120,000 subjects) and MDD (using a 10-fold leave-one-out procedure in the current sample), (ii) bivariate genomic-relationship-matrix restricted maximum likelihood (GREML) and (iii) SNP effect concordance analysis (SECA). With these methods, we found (i) that the EA-GPRS did not predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak negative genetic correlation with bivariate GREML analyses, but this correlation was not consistently significant, (iii) no evidence for concordance of MDD and EA SNP effects with SECA analysis. To conclude, our study confirms an association of lower EA and MDD risk, but this association was not because of measurable pleiotropic genetic effects, which suggests that environmental factors could be involved, for example, socioeconomic status.
    Matched MeSH terms: Gene-Environment Interaction
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