Analysis of case-control studies of genetic and environmental factors with missing genetic information and haplotype-phase ambiguity

BACKGROUND: Risk factors for Parkinson's disease (PD) can be more or less relevant to a population due to population-specific genetic architecture, local lifestyle habits, and environmental exposures. Therefore, it is essential to study PD at a local, regional, and continental scale in order to increase the knowledge on disease etiology. OBJECTIVE: We aimed to investigate the contribution of genetic and environmental factors to PD in a new Swedish case-control cohort. METHODS: PD patients (n=929) and matched population-based controls (n=935) from the southernmost county in Sweden were included in the cohort. Information on environmental exposures was obtained using questionnaires at inclusion. Genetic analyses included a genome-wide association study (GWAS), haplotype assessment, and a risk profile analysis using cumulative genetic risk scores. RESULTS: The cohort is a representative PD case-control cohort (64% men, mean age at diagnosis = 67 years, median Hoehn and Yahr score = 2.0), in which previously reported associations between PD and environmental factors, such as tobacco, could be confirmed. We describe the first GWAS of PD solely composed of PD patients from Sweden, and confirm associations to well-established risk alleles in SNCA. In addition, we identified a potential novel, population-specific PD risk variant in the PLPP4 locus (rs12771445) along with a risk haplotype in the region. CONCLUSIONS: This work provides an in-depth description of a new PD case-control cohort from southern Sweden in which we identified a potential novel PD risk locus, PLPP4. Replication studies are needed to determine whether the PLPP4 locus is associated with PD in Sweden, and on a global scale.

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Genetic and Environmental Factors Contributing to Parkinson's Disease: A Case-Control Study in the Cypriot Population

Frontiers in Neurology ◽

10.3389/fneur.2019.01047 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 1

Author(s):

Andrea Georgiou ◽

Christiana A. Demetriou ◽

Yiolanda P. Christou ◽

Alexandros Heraclides ◽

Eleni Leonidou ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Environmental Factors ◽

Case Control Study ◽

Case Control ◽

Genetic And Environmental Factors ◽

Control Study

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The Epidemiology of Childhood Cancers

European Oncology & Haematology ◽

10.17925/eoh.2009.05.1.79 ◽

2009 ◽

Vol 05 (01) ◽

pp. 79

Author(s):

Richard JQ McNally ◽

Keyword(s):

Risk Factors ◽

Alcohol Consumption ◽

Environmental Factors ◽

Case Control ◽

Childhood Cancers ◽

Hair Dyes ◽

Chemical Exposures ◽

Environmental Agents ◽

Genetic And Environmental Factors ◽

Parental Alcohol

In this article, the recent epidemiological literature on childhood cancer is reviewed. This includes findings from descriptive, case-control and cohort studies. The aetiology of most childhood cancers is unclear. Both genetic and environmental factors are likely to contribute. Increasing incidence, findings of clustering and seasonality in the incidence of certain cancers support a role for environmental agents in aetiology. The evidence concerning putative risk factors is considered and suggests that the aetiology is likely to be multifactorial and involve a number of different agents. These include infections, ionising radiation, certain chemical exposures, parental smoking, parental alcohol consumption and hair dyes. Conversely, breastfeeding and certain dietary supplements may convey protection. Recent findings regarding electromagnetic fields suggest that this factor is not likely to have a major role in aetiology.

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Association of FcεRIβ polymorphisms with risk of asthma and allergic rhinitis: evidence based on 29 case–control studies

Bioscience Reports ◽

10.1042/bsr20180177 ◽

2018 ◽

Vol 38 (4) ◽

Cited By ~ 2

Author(s):

Huanhuan Guo ◽

Tao Peng ◽

Ping Luo ◽

Huabin Li ◽

Shuo Huang ◽

...

Keyword(s):

Risk Factors ◽

Statistical Power ◽

Meta Analysis ◽

Allergic Diseases ◽

Case Control ◽

Nucleotide Polymorphisms ◽

Case Control Studies ◽

Potential Risk Factors ◽

Genetic And Environmental Factors ◽

The Stability

Purpose: Accumulating evidence has shown that allergic diseases are caused by a complex interaction of genetic and environmental factors, some single nucleotide polymorphisms (SNPs) existing in high-affinity IgE receptor β chain (FcεRIβ) are potential risk factors for allergic diseases. However, the results have been inconsistent and inconclusive due to the limited statistical power in individual study. Thus, we conducted a meta-analysis to systematically evaluate the association between FcεRIβ SNPs and allergic diseases risk. Methods: Eligible studies were collected from PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, and WanFang databases. Pooled odd ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated to assess the strength of the relationships between five polymorphisms (E237G, -109 C/T, RsaI_in2, RsaI_ex7, and I181L) and the risk of allergic diseases by using five genetic models. In addition, the stability of our analysis was evaluated by publication bias, sensitivity, and heterogeneity analysis. Results: Overall, a total of 29 case–control studies were included in this meta-analysis. We found that E237G (B vs. A: OR = 1.28, 95% CI = 1.06–1.53, P<0.001, I2 = 63.1%) and -109 C/T (BB vs. AA + AB: OR = 1.58, 95%CI = 1.26–1.98, P<0.001, I2 = 66.4%) were risk factors for allergic diseases. Conclusion: Our meta-analysis suggests that polymorphisms in FcεRIβ may be associated with the development of allergic diseases.

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Comparison of Different Haplotype-Based Haplotype-Based Association Methods for Gene-Environment (G×E) Interactions in Case-Control Studies when Haplotype-Phase Is Ambiguous

Human Heredity ◽

10.1159/000228923 ◽

2009 ◽

Vol 68 (4) ◽

pp. 252-267 ◽

Cited By ~ 4

Author(s):

Rebecca Hein ◽

Lars Beckmann ◽

Jenny Chang-Claude

Keyword(s):

Case Control ◽

Case Control Studies ◽

Gene Environment ◽

Haplotype Phase

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DRB1–environment interactions in multiple sclerosis etiology: results from two Swedish case–control studies

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2020-325676 ◽

2021 ◽

pp. jnnp-2020-325676

Author(s):

Anna Karin Hedström ◽

Jan Hillert ◽

Nicole Brenner ◽

Julia Butt ◽

Tim Waterboer ◽

...

Keyword(s):

Multiple Sclerosis ◽

Environmental Factors ◽

Environmental Factor ◽

Population Based ◽

Case Control ◽

Case Control Studies ◽

Adolescent Overweight ◽

Log Odds ◽

Antibody Levels ◽

Additive Scale

ObjectiveWe aimed to investigate the influence of environmental risk factors for multiple sclerosis (MS) in different genetic contexts, and study if interactions between environmental factors and human leucocyte antigen (HLA) genes differ in magnitude according to heterozygocity and homozygocity for HLA-DRB1*15:01.MethodsUsing population-based case–control studies (6985 cases, 6569 controls), subjects with different genotypes and smoking, EBNA-1 status and adolescent Body Mass status, were compared regarding MS risk, by calculating OR with 95% CI employing logistic regression. The interaction between different genotypes and each environmental factor was evaluated on the additive scale.ResultsThe effect of each DRB1*15:01 allele on MS risk was additive on the log-odds scale for each additional allele. Interaction between DRB1*15:01 and each assessed environmental factor was of similar magnitude regardless of the number of DRB1*15:01 alleles, although ORs were affected. When any of the environmental factors were present in DRB1*15:01 carriers without the protective A*02:01 allele, a three-way interaction occurred and rendered high ORs, especially among DRB1*15:01 homozygotes (OR 20.0, 95% CI 13.1 to 30.5 among smokers, OR 21.9, 95% CI 15.0 to 31.8 among those with elevated EBNA-1 antibody levels, and OR 44.3, 95% CI 13.5 to 145 among those who reported adolescent overweight/obesity).ConclusionsThe strikingly increased MS risk among DRB*15:01 homozygotes exposed to any of the environmental factors is a further argument in favour of these factors acting on immune-related mechanisms. The data further reinforce the importance of preventive measures, in particular for those with a genetic susceptibility to MS.

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