Genetic and Environmental Risk Factors for Keratoconus

Keratoconus, a progressive corneal ectasia, is a complex disease with both genetic and environmental risk factors. The exact etiology is not known and is likely variable between individuals. Conditions such as hay fever and allergy are associated with increased risk, while diabetes may be protective. Behaviors such as eye rubbing are also implicated, but direct causality has not been proven. Genetics plays a major role in risk for some individuals, with many large pedigrees showing autosomal inheritance patterns. Several genes have been implicated using linkage and follow-up sequencing in these families. Genome-wide association studies for keratoconus and for quantitative traits such as central corneal thickness have identified several genetic loci that contribute to a cumulative risk for keratoconus, even in people without a family history of the disease. Identification of risk genes for keratoconus is improving our understanding of the biology of this complex disease.

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Novel directions for G × E analysis in psychiatry

Epidemiology and Psychiatric Sciences ◽

10.1017/s2045796014000584 ◽

2014 ◽

Vol 24 (1) ◽

pp. 12-19 ◽

Cited By ~ 6

Author(s):

A. A. E. Vinkhuyzen ◽

N. R. Wray

Keyword(s):

Risk Factors ◽

Environmental Risk ◽

Large Scale ◽

Association Studies ◽

Environmental Risk Factors ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Model Framework ◽

Genome Wide ◽

Environmental Measures

G × E in psychiatry may explain why environmental risk factors have big impact in some individuals but not in others, and conversely why relatives that are genetically at risk for disease do not all develop disease. Here we discuss two novel methods that use an aggregate genome-wide measure of genetic risk to detect G × E and estimate its effect in the population using data currently available and data we anticipate will be available in the near future. The first method exploits summary statistics from large-scale genome-wide association studies ignorant of the environmental conditions and detects G × E in an out-of-sample risk-profiling framework. The second method relies on larger samples and is based on a mixed linear model framework. It estimates variance explained directly from single nucleotide polymorphisms and environmental measures. Both methods have great potential to improve public health interventions focusing on risk-based screening that is informed by both genetic and environmental risk factors.

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Evaluating the effects of alcohol and tobacco use on cardiovascular disease using multivariable Mendelian randomization

10.1101/757146 ◽

2019 ◽

Cited By ~ 1

Author(s):

Daniel B. Rosoff ◽

George Davey Smith ◽

Nehal Mehta ◽

Toni-Kim Clarke ◽

Falk W. Lohoff

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Alcohol Use ◽

Tobacco Use ◽

Mendelian Randomization ◽

Association Studies ◽

Density Lipoprotein ◽

Genome Wide Association Studies ◽

Cvd Risk ◽

Increased Risk

ABSTRACTAlcohol and tobacco use, two major modifiable risk factors for cardiovascular disease (CVD), are often consumed together. Using large publicly available genome-wide association studies (results from > 940,000 participants), we conducted two-sample multivariable Mendelian randomization (MR) to simultaneously assess the independent effects of alcohol and tobacco use on CVD risk factors and events. We found genetic instruments associated with increased alcohol use, controlling for tobacco use, associated with increased high-density-lipoprotein-cholesterol (HDL-C), decreased triglycerides, but not with coronary heart disease (CHD), myocardial infarction (MI), nor stroke; and instruments for increased tobacco use, controlling for alcohol use, associated with decreased HDL-C, increased triglycerides, and increased risk of CHD and MI. Exploratory analysis found associations with HDL-C, LDL-C, and intermediate-density-lipoprotein metabolites. Consistency of results across complementary methods accommodating different MR assumptions strengthened causal inference, providing strong genetic evidence for the causal effects of modifiable lifestyle risk factors on CVD risk.

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Genetic and Environmental Risk Factors for Intracerebral Hemorrhage

Stroke ◽

10.1161/str.32.suppl_1.321 ◽

2001 ◽

Vol 32 (suppl_1) ◽

pp. 321-321

Author(s):

Daniel Woo ◽

Laura Sauerbeck ◽

Brett M Kissela ◽

Jane C Khoury ◽

Rakesh Shukla ◽

...

Keyword(s):

Risk Factors ◽

Intracerebral Hemorrhage ◽

Environmental Risk ◽

Multivariable Analysis ◽

Population Based ◽

Environmental Risk Factors ◽

Degree Relative ◽

Increased Risk ◽

Apo E ◽

Apo E Genotype

27 Introduction: We report a planned midpoint analysis of a prospective, population-based, case-control study of the genetic and environmental risk factors of spontaneous, non-traumatic, intracerebral hemorrhage (ICH). Methods: Cases were matched to two controls by age, race and gender. Data was obtained by direct interview and review of all available medical and neuroimaging data. Apolipoprotein E (Apo E)genotype was determined by polymerase chain reaction. Multivariable analyses were performed using logistic regression modeling. Results: Between 6/97 and 2/00, 189 cases of ICH (150 white/39 black; 68 lobar/121 non-lobar) and 368 controls were enrolled into the study. Independent risk factors for multivariable analysis are listed in the table. Only prior stroke was an independent risk factor for both lobar and non-lobar ICH. Conclusions: The importance of individual genetic and environmental risk factors for ICH vary substantially by location of ICH. A history of a first-degree relative with ICH was associated with an increased risk of lobar ICH, independent of Apo E genotype. This finding indicates that other genetic risk factors may be important in the development of ICH.

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Genetics of Atrial Fibrillation in 2020

Circulation Research ◽

10.1161/circresaha.120.316575 ◽

2020 ◽

Vol 127 (1) ◽

pp. 21-33 ◽

Cited By ~ 4

Author(s):

Carolina Roselli ◽

Michiel Rienstra ◽

Patrick T. Ellinor

Keyword(s):

Atrial Fibrillation ◽

Complex Disease ◽

Association Studies ◽

Heart Rhythm ◽

Genome Wide Association Studies ◽

Future Directions ◽

Genetics Research ◽

Genome Wide ◽

Increased Risk ◽

Rhythm Disorder

Atrial fibrillation is a common heart rhythm disorder that leads to an increased risk for stroke and heart failure. Atrial fibrillation is a complex disease with both environmental and genetic risk factors that contribute to the arrhythmia. Over the last decade, rapid progress has been made in identifying the genetic basis for this common condition. In this review, we provide an overview of the primary types of genetic analyses performed for atrial fibrillation, including linkage studies, genome-wide association studies, and studies of rare coding variation. With these results in mind, we aim to highlighting the existing knowledge gaps and future directions for atrial fibrillation genetics research.

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Environmental Risk Factors for Pulmonary Mycobacterium avium-intracellulare Complex Disease

CHEST Journal ◽

10.1378/chest.10-2315 ◽

2011 ◽

Vol 140 (3) ◽

pp. 723-729 ◽

Cited By ~ 35

Author(s):

Koichi Maekawa ◽

Yutaka Ito ◽

Toyohiro Hirai ◽

Takeshi Kubo ◽

Seiichiro Imai ◽

...

Keyword(s):

Risk Factors ◽

Mycobacterium Avium ◽

Environmental Risk ◽

Complex Disease ◽

Environmental Risk Factors ◽

Mycobacterium Avium Intracellulare

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Modelling of time-to-events in an ambispective study: illustration with the analysis of ABO blood groups on venous thrombosis recurrence

10.1101/2021.11.20.21266583 ◽

2021 ◽

Author(s):

Gaëlle Munsch ◽

Louisa Goumidi ◽

Astrid van Hylckama Vlieg ◽

Manal Ibrahim-Kosta ◽

Maria Bruzelius ◽

...

Keyword(s):

Risk Factors ◽

Statistical Power ◽

Association Studies ◽

Blood Groups ◽

Genome Wide Association Studies ◽

Abo Blood Groups ◽

Genome Wide ◽

Increased Risk ◽

Independent Risk Factors ◽

Analyse Time

In studies of time-to-events, it is common to collect information about events that occurred before the inclusion in a prospective cohort. In an ambispective design, when the risk factors studied are independent of time, including both pre- and post-inclusion events in the analyses increases the statistical power but may lead to a selection bias. To avoid such a bias, we propose a survival analysis weighted by the inverse of the survival probability at the time of data collection about the events. This method is applied to the study of the association of ABO blood groups with the risk of venous thromboembolism (VT) recurrence in the MARTHA and MEGA cohorts. The former relying on an ambispective design and the latter on a standard prospective one. In the combined sample totalling 2,752 patients including 993 recurrences, compared with the O1 group, A1 has an increased risk (Hazard Ratio (HR) of 1.18, p=4.2x10-3), homogeneously in MARTHA and in MEGA. The same trend (HR=1.19, p=0.06) was observed for the less frequent A2 group. In conclusion, this work clarified the association of ABO blood groups with the risk of VT recurrence. Besides, the methodology proposed here to analyse time-independent risk factors of events in an ambispective design has an immediate field of application in the context of genome wide association studies.

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Occupational and environmental risk factors of idiopathic pulmonary fibrosis: a systematic review and meta-analyses

Scientific Reports ◽

10.1038/s41598-021-81591-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yeonkyung Park ◽

Chiwon Ahn ◽

Tae-Hyung Kim

Keyword(s):

Risk Factors ◽

Systematic Review ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Environmental Risk ◽

Environmental Risk Factors ◽

Cochrane Library ◽

Wood Dust ◽

Increased Risk ◽

Metal Dust

AbstractIdiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease of unknown cause. It has a high risk of rapid progression and mortality. We conducted a systematic review and meta-analysis to evaluate the risk factor of IPF. We searched Medline, Embase, and the Cochrane library from the earliest record to March, 2020. Case–control studies on occupational and environmental risk factors or on jobs with a risk of IPF were searched for. From 2490 relevant records, 12 studies were included. Any occupational or environmental exposure to metal dust (OR 1.83, 95% CI 1.15–2.91, I2 = 54%), wood dust (OR 1.62 5% CI 1.04–2.53, I2 = 5%) and pesticide (OR 2.07, 95% CI 1.24–3.45, I2 = 0%) were associated with an increased risk of IPF. Farming or agricultural work (OR 1.88, 95% CI 1.17–3.04, I2 = 67%) was also associated with an increased risk of IPF. Moreover, smoking increased IPF risk with an odds ratio of 1.39 (95% CI 1.01–1.91, I2 = 29%). In conclusion, metal dust, wood dust, pesticide, occupational history of farming or agriculture and ever smoking increased the risk of IPF.

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Maternal environmental risk factors for congenital hydrocephalus: a systematic review

Neurosurgical FOCUS ◽

10.3171/2016.8.focus16280 ◽

2016 ◽

Vol 41 (5) ◽

pp. E3 ◽

Cited By ~ 6

Author(s):

Aristotelis V. Kalyvas ◽

Theodosis Kalamatianos ◽

Mantha Pantazi ◽

Georgios D. Lianos ◽

George Stranjalis ◽

...

Keyword(s):

Risk Factors ◽

Environmental Risk ◽

Scientific Information ◽

Case Series ◽

Environmental Risk Factors ◽

Congenital Hydrocephalus ◽

Cochrane Library ◽

Related Risk ◽

Increased Risk ◽

The Impact

OBJECTIVE Congenital hydrocephalus (CH) is one of the most frequent CNS congenital malformations, representing an entity with serious pathological consequences. Although several studies have previously assessed child-related risk factors associated with CH development, there is a gap of knowledge on maternal environmental risk factors related to CH. The authors have systematically assessed extrinsic factors in the maternal environment that potentially confer an increased risk of CH development. METHODS The Cochrane Library, MEDLINE, and EMBASE were systematically searched for works published between 1966 and December 2015 to identify all relevant articles published in English. Only studies that investigated environmental risk factors concerning the mother—either during gestation or pregestationally—were included. RESULTS In total, 13 studies (5 cohorts, 3 case series, 3 case-control studies, 1 meta-analysis, and 1 case report) meeting the inclusion criteria were identified. Maternal medication or alcohol use during gestation; lifestyle modifiable maternal pathologies such as obesity, diabetes, or hypertension; lack of prenatal care; and a low socioeconomic status were identified as significant maternal environmental risk factors for CH development. Maternal infections and trauma to the mother during pregnancy have also been highlighted as potential mother-related risk factors for CH. CONCLUSIONS Congenital hydrocephalus is an important cause of serious infant health disability that can lead to health inequalities among adults. The present study identified several maternal environmental risk factors for CH, thus yielding important scientific information relevant to prevention of some CH cases. However, further research is warranted to confirm the impact of the identified factors and examine their underlying behavioral and/or biological basis, leading to the generation of suitable prevention strategies.

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“Environmental risk factors associated with juvenile idiopathic arthritis associated uveitis: a systematic review of the literature”

Journal of Ophthalmic Inflammation and Infection ◽

10.1186/s12348-021-00247-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sarah L. N. Clarke ◽

Katie S. Mageean ◽

Henry Carlton ◽

Gabriele Simonini ◽

Gemma C. Sharp ◽

...

Keyword(s):

Risk Factors ◽

Systematic Review ◽

Vitamin D ◽

Juvenile Idiopathic Arthritis ◽

Environmental Risk ◽

Environmental Risk Factors ◽

Inclusion Criteria ◽

Online Databases ◽

Increased Risk ◽

Predominantly Female

Abstract Background Juvenile idiopathic arthritis associated uveitis (JIA-U) is the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA) and carries considerable risk to vision. The aim of this systematic review was to synthesise evidence of environmental risk factors for JIA-U and identify risk factors which may be modifiable or used to stratify JIA patients. Methods This systematic review was carried out in accordance with PRISMA guidelines. Four online databases - Cumulative Index of Nursing and Allied Health Literature, Web of Science, MEDLINE and Embase - were searched from database inception to 12th August 2020. Identified studies were screened by two independent reviewers against pre-defined inclusion and exclusion criteria. Data was extracted from all primary studies meeting inclusion criteria and independently checked. Results We identified three studies from 895 unique records which met the inclusion criteria, each examining a different environmental risk factor. This systematic review includes 973, predominantly female, participants with JIA across these three studies. The use of allergy medication or documentation of “allergy”/“allergic” in the medical records was associated with an increased risk of JIA-U in all models presented. Vitamin D sufficiency was associated with reduced risk of JIA-U. There was insufficient evidence to support an association between seasonality and JIA-U. Conclusions This review identifies a potential role for allergy and vitamin D in JIA-U. It also illustrates the paucity of data regarding environmental risk factors for JIA-U and highlights the need for further research to both identify additional risk factors and replicate existing findings.

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A life course perspective on familial and environmental risks for schizophrenia using a western Australian E-cohort

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.868 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S35-S35

Author(s):

V. Morgan ◽

P. Di Prinzio ◽

G. Valuri ◽

M. Croft ◽

S. Shah ◽

...

Keyword(s):

Risk Factors ◽

Environmental Risk ◽

Psychotic Disorders ◽

Familial Risk ◽

Environmental Risk Factors ◽

Life Course Perspective ◽

Environmental Stressors ◽

Psychotic Illness ◽

Increased Risk ◽

Timing Of Exposure

IntroductionFamilial risk for psychosis may interact with environmental risk factors.ObjectivesWe are studying a large birth cohort of children of mothers with psychotic disorders, themselves at high risk of developing a psychotic illness, to understand the developmental aetiology of psychotic illness.AimsOur aim is to examine whether exposure to environmental stressors in childhood, including timing of exposure, is a risk factor for psychotic illness, independent of familial liability. Specificity to maternal schizophrenia is explored.MethodsWe used record-linkage across state-wide registers (midwives, psychiatric, child protection and mortality, among others) to identify 15,486 offspring born in Western Australia 1980–2001 to mothers with a lifetime history of psychotic illness (case children) and compared them with 452,459 offspring born in the same period to mothers with no known psychiatric history (comparison children).ResultsA total of 4.1% of case children had developed a psychotic illness compared to 1.1% of comparison children. Exposure to environmental risk factors including obstetric complications, aboriginality, lower socioeconomic status, discontinuity in parenting and childhood abuse significantly increased risk of psychotic illness in offspring. Length and age at time of discontinuity in parenting impacted on risk. At the same time, case children were also significantly more likely than comparison children to be at risk of experiencing these adverse life events.ConclusionsExposure to environmental stressors is associated with psychotic illness, and timing of exposure is important. However, children already at increased familial risk for psychotic illness are also at increased risk of experiencing these environmental stressors.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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