Coffee, Genetic Variants, and Parkinson's Disease: Gene-Environment Interactions.
Ontology highlight
ABSTRACT:
SUBMITTER: Yamada-Fowler N
PROVIDER: S-EPMC4350262 | biostudies-literature | 2015 Mar
REPOSITORIES: biostudies-literature
Publications
Coffee, Genetic Variants, and Parkinson's Disease: Gene-Environment Interactions.
Yamada-Fowler Naomi N Söderkvist Peter P
Journal of caffeine research 20150301 1
Studies of gene-environment interactions may help us to understand the disease mechanisms of common and complex diseases such as Parkinson's disease (PD). Sporadic PD, the common form of PD, is thought to be a multifactorial disorder caused by combinations of multiple genetic factors and environmental or life-style exposures. Since one of the most extensively studied life-style factors in PD is coffee/caffeine intake, here, the studies of genetic polymorphisms with life-style interactions of spo ...[more]
Similar Datasets
Project description:Drinking caffeinated coffee has been reported to provide protection against Parkinson's disease (PD). Caffeine is an adenosine A2A receptor (encoded by the gene ADORA2A) antagonist that increases dopaminergic neurotransmission and Cytochrome P450 1A2 (gene: CYP1A2) metabolizes caffeine; thus, gene polymorphisms in ADORA2A and CYP1A2 may influence the effect coffee consumption has on PD risk.In a population-based case-control study (PASIDA) in Denmark (1,556 PD patients and 1,606 birth year- and gender-matched controls), we assessed interactions between lifetime coffee consumption and 3 polymorphisms in ADORA2A and CYP1A2 for all subjects, and incident and prevalent PD cases separately using logistic regression models. We also conducted a meta-analysis combining our results with those from previous studies.We estimated statistically significant interactions for ADORA2A rs5760423 and heavy vs. light coffee consumption in incident (OR interaction = 0.66 [95% CI 0.46-0.94], p = 0.02) but not prevalent PD. We did not observe interactions for CYP1A2 rs762551 and rs2472304 in incident or prevalent PD. In meta-analyses, PD associations with daily coffee consumption were strongest among carriers of variant alleles in both ADORA2A and CYP1A2.We corroborated results from a previous report that described interactions between ADORA2A and CYP1A2 polymorphisms and coffee consumption. Our results also suggest that survivor bias may affect results of studies that enroll prevalent PD cases.
| S-EPMC5465963 | biostudies-literature
Project description:Diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) arise from complex interactions of genetic and environmental factors, with genetic variants regulating individual responses to environmental exposures (i.e. gene-by-environment interactions). Identifying gene-by-environment interactions will be critical to fully understanding disease mechanisms and developing personalized therapeutics, though these interactions are still poorly understood and largely under-studied. Candidate gene approaches have shown that known disease risk variants often regulate response to environmental factors. However, recent improvements in exposome- and genome-wide association and interaction studies in humans and mice are enabling discovery of novel genetic variants and pathways that predict response to a variety of environmental factors. Here, we highlight recent approaches and ongoing developments in human and rodent studies to identify genetic modulators of environmental factors using AD and PD as exemplars. Identifying gene-by-environment interactions in disease will be critical to developing personalized intervention strategies and will pave the way for precision medicine.
| S-EPMC6700747 | biostudies-literature
Project description:Prior studies causally linked mutations in SNCA, MAPT, and LRRK2 genes with familial Parkinsonism. Genome-wide association studies have demonstrated association of single nucleotide polymorphisms (SNPs) in those three genes with sporadic Parkinson's disease (PD) susceptibility worldwide. Here we investigated the interactions between SNPs in those three susceptibility genes and environmental exposures (pesticides application, tobacco smoking, coffee drinking, and alcohol drinking) also associated with PD susceptibility.Pairwise interactions between environmental exposures and 18 variants (16 SNPs and two variable number tandem repeats, or "VNTRs") in SNCA, MAPT and LRRK2, were investigated using data from 1098 PD cases from the upper Midwest, USA and 1098 matched controls. Environmental exposures were assessed using a validated telephone interview script.Five pairwise interactions had uncorrected P-values < 0.05. These included pairings of pesticides × SNCA rs3775423 or MAPT rs4792891, coffee drinking × MAPT H1/H2 haplotype or MAPT rs16940806, and alcohol drinking × MAPT rs2435211. None of these interactions remained significant after Bonferroni correction. Secondary analyses in strata defined by type of control (sibling or unrelated), sex, or age at onset of the case also did not identify significant interactions after Bonferroni correction.This study documented limited pairwise interactions between established genetic and environmental risk factors for PD; however, the associations were not significant after correction for multiple testing.
| S-EPMC4685949 | biostudies-literature
Project description:Summary Gene-by-environment (GxE) interactions, in which a genetic variant’s phenotypic effect is condition specific, are fundamental for understanding fitness landscapes and evolution but have been difficult to identify at the single-nucleotide level. Although many condition-specific quantitative trait loci (QTLs) have been mapped, these typically contain numerous inconsequential variants in linkage, precluding understanding of the causal GxE variants. Here, we introduce BARcoded Cas9 retron precise parallel editing via homology (CRISPEY-BAR), a high-throughput precision genome editing strategy, and use it to map GxE interactions of naturally occurring genetic polymorphisms impacting yeast growth. We identified hundreds of GxE variants within condition-specific QTLs, revealing unexpected genetic complexity. Moreover, we found that 93.7% of non-neutral natural variants within ergosterol biosynthesis pathway genes showed GxE interactions, including many impacting antifungal drug resistance through diverse molecular mechanisms. In sum, our results suggest an extremely complex, context-dependent fitness landscape characterized by pervasive GxE interactions while also demonstrating massively parallel genome editing as an effective means for investigating this complexity. Graphical abstract Highlights • CRISPEY-BAR precisely measures effects of single genetic variants in high throughput• Pooled competition of barcoded strains maps condition-specific (GxE) fitness effects• Editing more than 4,000 natural genetic variants reveals pervasive GxE and molecular mechanisms• Many natural GxE variants in the ergosterol pathway lead to antifungal drug resistance Chen et al. introduce CRISPEY-BAR, a method to precisely measure individual genetic variant effects through massively parallel genome editing. Editing more than 4,000 natural genetic variants in yeast, they found pervasive condition-specific effects known as gene-by-environment (GxE) interactions. The single-nucleotide resolution revealed many GxE variants underlying antifungal drug resistance and their molecular mechanisms.
| S-EPMC10112290 | biostudies-literature
Project description:Parkinson's disease is now the most rapidly growing neurodegenerative disease worldwide. It is therefore critical to identify which factors, and to what extent, contribute to the multifactorial etiology of Parkinson's disease. Here, we address two interesting elements from the perspective of genetics, namely (a) the estimated age of several genetic risk factors related to Parkinson's disease; and (b) the relative contribution of genetics to the etiology of Parkinson's disease, as derived from twin studies. Based on these two perspectives, we argue that most genetic risk factors are by themselves insufficient to explain the majority of Parkinson's disease, and that environmental factors are required for these genetic factors to become pathophysiologically relevant.
| S-EPMC10741370 | biostudies-literature
Project description:ObjectivesTo investigate associations of Parkinson's disease (PD) and parkinsonian syndromes with polymorphic genes that influence metabolism of either foreign chemical substances or dopamine and to seek evidence of gene-environment interaction effects that modify risk.MethodsA case-control study of 959 prevalent cases of parkinsonism (767 with PD) and 1989 controls across five European centres. Occupational hygienists estimated the average annual intensity of exposure to solvents, pesticides and metals, (iron, copper, manganese), blind to disease status. CYP2D6, PON1, GSTM1, GSTT1, GSTM3, GSTP1, NQO1, CYP1B1, MAO-A, MAO-B, SOD 2, EPHX, DAT1, DRD2 and NAT2 were genotyped. Results were analysed using multiple logistic regression adjusting for key confounders.ResultsThere was a modest but significant association between MAO-A polymorphism in males and disease risk (G vs T, OR 1.30, 95% CI 1.02 to 1.66, adjusted). The majority of gene-environment analyses did not show significant interaction effects. There were possible interaction effects between GSTM1 null genotype and solvent exposure (which were stronger when limited to PD cases only).ConclusionsMany small studies have reported associations between genetic polymorphisms and PD. Fewer have examined gene-environment interactions. This large study was sufficiently powered to examine these aspects. GSTM1 null subjects heavily exposed to solvents appear to be at increased risk of PD. There was insufficient evidence that the other gene-environment combinations investigated modified disease risk, suggesting they contribute little to the burden of PD.
| S-EPMC2078383 | biostudies-literature
Project description:OBJECTIVE:To systematically investigate the association of environmental risk factors and prodromal features with incident Parkinson's disease (PD) diagnosis and the interaction of genetic risk with these factors. To evaluate whether existing risk prediction algorithms are improved by the inclusion of genetic risk scores. METHODS:We identified individuals with an incident diagnosis of PD (n=1276) and controls (n=500?406) in UK Biobank. We determined the association of risk factors with incident PD using adjusted logistic regression models. We constructed polygenic risk scores (PRSs) using external weights and selected the best PRS from a subset of the cohort (30%). The PRS was used in a separate testing set (70%) to examine gene-environment interactions and compare predictive models for PD. RESULTS:Strong evidence of association (false discovery rate <0.05) was found between PD and a positive family history of PD, a positive family history of dementia, non-smoking, low alcohol consumption, depression, daytime somnolence, epilepsy and earlier menarche. Individuals with the highest 10% of PRSs had increased risk of PD (OR 3.37, 95%?CI 2.41 to 4.70) compared with the lowest risk decile. A higher PRS was associated with earlier age at PD diagnosis and inclusion of the PRS in the PREDICT-PD algorithm led to a modest improvement in model performance. We found evidence of an interaction between the PRS and diabetes. INTERPRETATION:Here, we used UK Biobank data to reproduce several well-known associations with PD, to demonstrate the validity of a PRS and to demonstrate a novel gene-environment interaction, whereby the effect of diabetes on PD risk appears to depend on background genetic risk for PD.
| S-EPMC7509524 | biostudies-literature
Project description:Our aim was to identify genes that influence the inverse association of coffee with the risk of developing Parkinson's disease (PD). We used genome-wide genotype data and lifetime caffeinated-coffee-consumption data on 1,458 persons with PD and 931 without PD from the NeuroGenetics Research Consortium (NGRC), and we performed a genome-wide association and interaction study (GWAIS), testing each SNP's main-effect plus its interaction with coffee, adjusting for sex, age, and two principal components. We then stratified subjects as heavy or light coffee-drinkers and performed genome-wide association study (GWAS) in each group. We replicated the most significant SNP. Finally, we imputed the NGRC dataset, increasing genomic coverage to examine the region of interest in detail. The primary analyses (GWAIS, GWAS, Replication) were performed using genotyped data. In GWAIS, the most significant signal came from rs4998386 and the neighboring SNPs in GRIN2A. GRIN2A encodes an NMDA-glutamate-receptor subunit and regulates excitatory neurotransmission in the brain. Achieving P(2df)?=?10(-6), GRIN2A surpassed all known PD susceptibility genes in significance in the GWAIS. In stratified GWAS, the GRIN2A signal was present in heavy coffee-drinkers (OR?=?0.43; P?=?6×10(-7)) but not in light coffee-drinkers. The a priori Replication hypothesis that "Among heavy coffee-drinkers, rs4998386_T carriers have lower PD risk than rs4998386_CC carriers" was confirmed: OR(Replication)?=?0.59, P(Replication)?=?10(-3); OR(Pooled)?=?0.51, P(Pooled)?=?7×10(-8). Compared to light coffee-drinkers with rs4998386_CC genotype, heavy coffee-drinkers with rs4998386_CC genotype had 18% lower risk (P?=?3×10(-3)), whereas heavy coffee-drinkers with rs4998386_TC genotype had 59% lower risk (P?=?6×10(-13)). Imputation revealed a block of SNPs that achieved P(2df)<5×10(-8) in GWAIS, and OR?=?0.41, P?=?3×10(-8) in heavy coffee-drinkers. This study is proof of concept that inclusion of environmental factors can help identify genes that are missed in GWAS. Both adenosine antagonists (caffeine-like) and glutamate antagonists (GRIN2A-related) are being tested in clinical trials for treatment of PD. GRIN2A may be a useful pharmacogenetic marker for subdividing individuals in clinical trials to determine which medications might work best for which patients.
| S-EPMC3158052 | biostudies-literature
Project description:Estimated heritability of coffee intake ranges from 0.36 to 0.58, however, these point estimates assume that inherited effects are the same throughout the distribution of coffee intake, i.e., whether consumption is high or low relative to intake in the population. Quantile regression of 4788 child-parent pairs and 2380 siblings showed that offspring-parent and sibling concordance became progressively greater with increasing quantiles of coffee intake. Each cup/day increase in the parents' coffee intake was associated with an offspring increase of 0.020?±?0.013 cup/day at the 10th percentile of the offsprings' coffee intake (slope?±?SE, NS), 0.137?±?0.034 cup/day at their 25th percentile (P?=?5.2?×?10-5), 0.159?±?0.029 cup/day at the 50th percentile (P?=?5.8?×?10-8), 0.233?±?0.049 cup/day at the 75th percentile (P?=?1.8?×?10-6), and 0.284?±?0.054 cup/day at the 90th percentile (P?=?1.2?×?10-7). This quantile-specific heritability suggests that factors that distinguish heavier vs. lighter drinkers (smoking, male sex) will likely manifest differences in estimated heritability, as reported.
| S-EPMC7531626 | biostudies-literature
Project description:Genetic variants of leucine-rich repeat kinase 2 (LRRK2) were reported to alter the risk for Parkinson's disease (PD). However, the genetic spectrum of LRRK2 variants has not been clearly disclosed yet in Taiwanese population. Herein, we sequenced LRRK2 coding region in 70 Taiwanese early onset PD patients (age at onset ≤ 50), and found six amino acid-changing single nucleotide polymorphisms (SNPs, N551K, R1398H, R1628P, S1647T, G2385R and M2397T), one reported (R1441H) and 2 novel missense (R767H and S885N) mutations. We examined the frequency of identified LRRK2 variants by genotyping 573 Taiwanese patients with PD and 503 age-matched control subjects. The results showed that PD patients demonstrated a higher frequency of G2385R A allele (4.6%) than control subjects (2.1%; odds ratio = 2.27, 95% confidence interval: 1.38-3.88, P = 0.0017). Fewer PD patients (27.7%) carried the 1647T-2397T haplotype as compared with the control subjects (33.0%; odds ratio = 0.80, 95% confidence interval: 0.65-0.97, P = 0.0215). However, the frequency of 1647T-2385R-2397T haplotype (4.3%) in PD patients was still higher than in control subjects (1.9%, odds ratio: 2.15, 95% confidence interval: 1.27-3.78, P = 0.0058). While no additional subject was found to carry R767H and R1441H, one more patient was observed to carry the S885N variant. Our results indicate a robust risk association regarding G2385R and a new possible protective haplotype (1647T-2397T). Gene-environmental interaction and a larger cohort study are warranted to validate our findings. Additionally, two new missense mutations (R767H and S885N) regarding LRRK2 in PD patients were identified. Functional studies are needed to elucidate the effects of these LRRK2 variants on protein function.
| S-EPMC3855417 | biostudies-literature