The Epidemiology of the Genetic Liability for Schizophrenia

2000 ◽  
Vol 34 (1_suppl) ◽  
pp. A47-A55 ◽  
Author(s):  
Joachim Hallmayer
Keyword(s):  
Large Scale ◽  
Genetic Factors ◽  
Association Studies ◽  
Molecular Genetic ◽  
Positive Family History ◽  
Adoption Studies ◽  
Genetic Liability ◽  
Risk Increase ◽  
Increased Risk ◽  
Prevention Trials

Objective The low incidence of schizophrenia prohibits large scale prevention trials, and the question arises whether such studies become more feasible by taking into account genetic factors. The aim of the paper was to inform preventive endeavours with an account of the genetic background to schizophrenia. Method The family, twin and adoptive studies of schizophrenia are reviewed and recent molecular genetic data presented. Results Children of a parent diagnosed with schizophrenia have a ten-fold increased risk of developing the disorder. Twin and adoption studies strongly suggest the risk increase is mainly due to genetic factors. On an individual level, a positive family history is the strongest known risk factor for schizophrenia. For a prevention study, very large numbers of families have to be screened in order to reach a sufficient sample size. Conclusions One obvious way to increase the accuracy of predicting who is at high risk of developing schizophrenia would be to find specific mutations in the human genome. Attempts to isolate specific genes by means of linkage and association studies have been unsuccessful so far and, given the number of genes involved, it is extremely unlikely that the predictive value of individual genes will be high enough to warrant intervention. Genetic studies also suggest the genetic liability extends beyond the traditional clinical phenotypes. Prevention trials might become possible by adopting a broader approach.

scholarly journals Exploration of Lung Cancer-Related Genetic Factors via Mendelian Randomization Method Based on Genomic and Transcriptomic Summarized Data

2021 ◽  
Vol 9 ◽  
Author(s):  
Nitao Cheng ◽  
Xinran Cui ◽  
Chen Chen ◽  
Changsheng Li ◽  
Jingyu Huang
Keyword(s):  
Lung Cancer ◽  
Lung Carcinoma ◽  
Large Scale ◽  
Genetic Factors ◽  
Mendelian Randomization ◽  
Familial Aggregation ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Increased Risk ◽  
The Impact

Lung carcinoma is one of the most deadly malignant tumors in mankind. With the rising incidence of lung cancer, searching for the high effective cures become more and more imperative. There has been sufficient research evidence that living habits and situations such as smoking and air pollution are associated with an increased risk of lung cancer. Simultaneously, the influence of individual genetic susceptibility on lung carcinoma morbidity has been confirmed, and a growing body of evidence has been accumulated on the relationship between various risk factors and the risk of different pathological types of lung cancer. Additionally, the analyses from many large-scale cancer registries have shown a degree of familial aggregation of lung cancer. To explore lung cancer-related genetic factors, Genome-Wide Association Studies (GWAS) have been used to identify several lung cancer susceptibility sites and have been widely validated. However, the biological mechanism behind the impact of these site mutations on lung cancer remains unclear. Therefore, this study applied the Summary data-based Mendelian Randomization (SMR) model through the integration of two GWAS datasets and four expression Quantitative Trait Loci (eQTL) datasets to identify susceptibility genes. Using this strategy, we found ten of Single Nucleotide Polymorphisms (SNPs) sites that affect the occurrence and development of lung tumors by regulating the expression of seven genes. Further analysis of the signaling pathway about these genes not only provides important clues to explain the pathogenesis of lung cancer but also has critical significance for the diagnosis and treatment of lung cancer.

scholarly journals Molecular genetics of bipolar disorder

2001 ◽  
Vol 178 (S41) ◽  
pp. s128-s133 ◽  
Author(s):  
Nick Craddock ◽  
Ian Jones
Keyword(s):  
Bipolar Disorder ◽  
Candidate Gene ◽  
Molecular Genetics ◽  
Ethical Issues ◽  
Association Studies ◽  
Single Gene ◽  
Molecular Genetic ◽  
Genetic Dissection ◽  
Adoption Studies ◽  
Candidate Gene Association

BackgroundA robust body of evidence from family, twin and adoption studies demonstrates the importance of genes in the pathogenesis of bipolar disorder. Recent advances in molecular genetics have made it possible to identify these susceptibility genes.AimsTo present an overview for clinical psychiatrists.MethodReview of current molecular genetics approaches and emerging findings.ResultsOccasional families may exist in which a single gene plays a major role in determining susceptibility, but the majority of bipolar disorder involves more complex genetic mechanisms such as the interaction of multiple genes and environmental factors. Molecular genetic positional and candidate gene approaches are being used for the genetic dissection of bipolar disorder. No gene has yet been identified but promising findings are emerging. Regions of interest include chromosomes 4p16, 12q23–q24, 16p13, 21q22, and Xq24–q26. Candidate gene association studies are in progress but no robust positive findings have yet emerged.ConclusionIt is almost certain that over the next few years the identification of bipolar susceptiblity genes will have a major impact on our understanding of disease pathophysiology. This is likely to lead to major improvements and treatment in patient care, but will also raise important ethical issues.

scholarly journals A description of large-scale metabolomics studies: increasing value by combining metabolomics with genome-wide SNP genotyping and transcriptional profiling

2012 ◽  
Vol 215 (1) ◽  
pp. 17-28 ◽  
Author(s):  
Georg Homuth ◽  
Alexander Teumer ◽  
Uwe Völker ◽  
Matthias Nauck
Keyword(s):  
Blood Cells ◽  
Large Scale ◽  
Genetic Factors ◽  
Association Studies ◽  
Transcriptional Profiling ◽  
Genome Wide Association Studies ◽  
Protein Levels ◽  
Future Developments ◽  
Genome Wide ◽  
Metabolome Data

The metabolome, defined as the reflection of metabolic dynamics derived from parameters measured primarily in easily accessible body fluids such as serum, plasma, and urine, can be considered as the omics data pool that is closest to the phenotype because it integrates genetic influences as well as nongenetic factors. Metabolic traits can be related to genetic polymorphisms in genome-wide association studies, enabling the identification of underlying genetic factors, as well as to specific phenotypes, resulting in the identification of metabolome signatures primarily caused by nongenetic factors. Similarly, correlation of metabolome data with transcriptional or/and proteome profiles of blood cells also produces valuable data, by revealing associations between metabolic changes and mRNA and protein levels. In the last years, the progress in correlating genetic variation and metabolome profiles was most impressive. This review will therefore try to summarize the most important of these studies and give an outlook on future developments.

scholarly journals The genetic epidemiology of personality disorders

2010 ◽  
Vol 12 (1) ◽  
pp. 103-114 ◽  
Keyword(s):  
Personality Disorders ◽  
Genetic Factors ◽  
Association Studies ◽  
Molecular Genetic ◽  
Cluster Structure ◽  
Epidemiologic Studies ◽  
Axis Ii ◽  
Candidate Gene Association ◽  
Axis I ◽  
Dsm Iv

Genetic epidemiologic studies indicate that all ten personality disorders (PDs) classified on the DSM-IV axis II are modestly to moderately heritable. Shared environmental and nonadditive genetic factors are of minor or no importance. No sex differences have been identified, Multivariate studies suggest that the extensive comorbidity between the PDs can be explained by three common genetic and environmental risk factors. The genetic factors do not reflect the DSM-IV cluster structure, but rather: i) broad vulnerability to PD pathology or negative emotionality; ii) high impulsivity/low agreeableness; and iii) introversion. Common genetic and environmental liability factors contribute to comorbidity between pairs or clusters of axis I and axis II disorders. Molecular genetic studies of PDs, mostly candidate gene association studies, indicate that genes linked to neurotransmitter pathways, especially in the serotonergic and dopaminergic systems, are involved. Future studies, using newer methods like genome-wide association, might take advantage of the use of endophenotypes.

scholarly journals An atlas of polygenic risk score associations to highlight putative causal relationships across the human phenome

2018 ◽  
Author(s):  
Tom G. Richardson ◽  
Sean Harrison ◽  
Gibran Hemani ◽  
George Davey Smith
Keyword(s):  
Web Application ◽  
Large Scale ◽  
Complex Disease ◽  
Association Studies ◽  
Risk Scores ◽  
Polygenic Risk Score ◽  
Genome Wide Association Studies ◽  
Genetic Liability ◽  
Polygenic Risk ◽  
The Uk

AbstractThe age of large-scale genome-wide association studies (GWAS) has provided us with an unprecedented opportunity to evaluate the genetic liability of complex disease using polygenic risk scores (PRS). In this study, we have analysed 162 PRS (P<5×l0 05) derived from GWAS and 551 heritable traits from the UK Biobank study (N=334,398). Findings can be investigated using a web application (http://mrcieu.mrsoftware.org/PRS_atlas/), which we envisage will help uncover both known and novel mechanisms which contribute towards disease susceptibility.To demonstrate this, we have investigated the results from a phenome-wide evaluation of schizophrenia genetic liability. Amongst findings were inverse associations with measures of cognitive function which extensive follow-up analyses using Mendelian randomization (MR) provided evidence of a causal relationship. We have also investigated the effect of multiple risk factors on disease using mediation and multivariable MR frameworks. Our atlas provides a resource for future endeavours seeking to unravel the causal determinants of complex disease.

scholarly journals Pedigree Analysis of Idiopathic Epilepsy In Children of South Kerala

2012 ◽  
Vol 01 (01) ◽  
pp. 024-029
Author(s):  
Amar Jayanthi. A.
Keyword(s):  
Genetic Factors ◽  
Age Of Onset ◽  
Association Studies ◽  
Positive Family History ◽  
Susceptibility Gene ◽  
Pedigree Analysis ◽  
Idiopathic Epilepsy ◽  
Major Health Problem ◽  
Neurology Clinic ◽  
Mode Of Inheritance

Abstract Background and aims: Epilepsy is a major health problem in infancy and childhood. Genetic factors are implicated in the etiology of epilepsy. A familial susceptibility to seizures have been recognized but the exact mode of inheritance remains unclear. The chief objective was to determine the inheritance pattern and to correlate its prevalence among closer relatives on the basis of sex, degree of relationship and age of onset of the disease. Materials and methods: A pedigree analysis of 100 clinically diagnosed children with idiopathic epilepsy seen between 1994 and 1997 at the Paediatric Neurology Clinic of Government Medical College, Thiruvananthapuram was done. The mode of inheritance was tested according to the genetic hypothesis of segregation analysis. Results: Positive family history was observed in 49% of the probands. A high proportion of probands with an early onset of disease showed involvement of family members and a significant sex predisposition for females was obtained. Relatives of female probands were affected more than those of males. Mothers were found to transmit the disease to offsprings more than the epileptic fathers. Conclusion: The results of pedigree analysis supported the hypothesis of an autosomal multifactorial mode of inheritance, with 86% heritability and a lower threshold for the disease to manifest. The application of modern genetic principles like identification of susceptibility gene to epilepsy, linkage and association studies would advance our understanding of the etiology of seizure disorders. Genetic factors may play a major role in the predisposition of relatives to epilepsy in families of probands with idiopathic epilepsy. The present study may aid in the genetic counselling of parents with epilepsy.

Molecular genetic pathways in Parkinson's disease: a review

2005 ◽  
Vol 109 (4) ◽  
pp. 355-364 ◽  
Author(s):  
Shushant Jain ◽  
Nicholas W. Wood ◽  
Daniel G. Healy
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Basis ◽  
Genetic Factors ◽  
Molecular Genetic ◽  
Mendelian Genetics ◽  
Susceptibility Factors ◽  
Increased Risk ◽  
Major Progress ◽  
Made In

Major progress has been made in the last decade in understanding the genetic basis of PD (Parkinson's disease) with five genes unequivocally associated with disease. As a result, multiple pathways have been implicated in the pathogenesis of PD, including proteasome impairment and mitochondrial dysfunction. Although Mendelian genetics has been successful in establishing a genetic predisposition for familial PD, this has not been reiterated in the sporadic form. In fact no genetic factors have been unequivocally associated with increased risk for sporadic PD. The difficulty in identifying susceptibility factors in PD has not only been because of numerous underpowered studies, but we have been unable to dissect out the genetic component in a multifactorial disease. This review aims to summarize the genetic findings within PD.

scholarly journals A Review of the Hereditary Component of Triple Negative Breast Cancer: High- and Moderate-Penetrance Breast Cancer Genes, Low-Penetrance Loci, and the Role of Nontraditional Genetic Elements

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Darrell L. Ellsworth ◽  
Clesson E. Turner ◽  
Rachel E. Ellsworth
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Large Scale ◽  
Triple Negative ◽  
Association Studies ◽  
African Ancestry ◽  
Genome Wide Association Studies ◽  
Genetic Elements ◽  
Genome Wide ◽  
Increased Risk

Triple negative breast cancer (TNBC), representing 10-15% of breast tumors diagnosed each year, is a clinically defined subtype of breast cancer associated with poor prognosis. The higher incidence of TNBC in certain populations such as young women and/or women of African ancestry and a unique pathological phenotype shared between TNBC and BRCA1-deficient tumors suggest that TNBC may be inherited through germline mutations. In this article, we describe genes and genetic elements, beyond BRCA1 and BRCA2, which have been associated with increased risk of TNBC. Multigene panel testing has identified high- and moderate-penetrance cancer predisposition genes associated with increased risk for TNBC. Development of large-scale genome-wide SNP assays coupled with genome-wide association studies (GWAS) has led to the discovery of low-penetrance TNBC-associated loci. Next-generation sequencing has identified variants in noncoding RNAs, viral integration sites, and genes in underexplored regions of the human genome that may contribute to the genetic underpinnings of TNBC. Advances in our understanding of the genetics of TNBC are driving improvements in risk assessment and patient management.

GENETIC FACTORS OF ALCOHOLIC PSYCHOSIS DEVELOPMENT

2021 ◽  
pp. 12-15
Author(s):  
Н.Ж. НУРМАНОВА ◽  
К.О. КЕНЖЕЕВА
Keyword(s):  
Dna Markers ◽  
Genetic Factors ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Ethanol Metabolism ◽  
Increased Risk ◽  
Genetic Level ◽  
Level 1 ◽  
Alcohol Psychosis ◽  
Biological Predisposition

Известно, что наследственную предрасположенность к алкоголизму на фенотипическом уровне можно изучать с помощью генетических маркеров, возможно отражающих их связь с заболеванием [2, 3]. Многие авторы говорят о существовании биологической предрасположенности к алкоголизму, закрепленной на генетическом уровне [1, 4, 5, 6], однако природа и механизмы наследования при алкогольных психозах до настоящего времени остаются неясными. Цель настоящей работы - поиск маркеров повышенного риска развития алкогольных психозов путем проведения молекулярно-генетического анализа ДНК-маркеров основных ферментов метаболизма этанола It is known that the hereditary predisposition to alcoholism at the phenotypic level can be studied with the help of genetic markers, possibly reflecting their connection with the disease [2, 3]. Many authors say that there is a biological predisposition to alcoholism, fixed at the genetic level [1, 4, 5, 6], However, the nature and mechanisms of inheritance in alcoholic psychoses are still unclear. The aim of this work is to search for markers of increased risk of alcohol psychosis by conducting molecular genetic analysis of DNA markers of the main enzymes of ethanol metabolism.

Abstract 19297: Susceptibility Loci for Clinical CAD Predispose to Subclinical Coronary Atherosclerosis Throughout the Life Course

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Elias Salfati ◽  
Shuktika Nandkeolyar ◽  
Stephen Fortmann ◽  
Stephen Sidney ◽  
Mark A Hlakty ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Life Course ◽  
Coronary Atherosclerosis ◽  
Large Scale ◽  
Association Studies ◽  
Subclinical Atherosclerosis ◽  
Genetic Risk Score ◽  
Genome Wide Association Studies ◽  
Increased Risk ◽  
The Life Course

Recent genome wide association studies (GWAS) have identified 49 single nucleotide polymorphisms (SNPs) associated with clinically significant complications of CAD including myocardial infarction (MI), CABG, PCI, and/or angina. The mechanism by which these loci influence the risk of clinical CAD remains largely unclear. We hypothesized that variants at these loci collectively facilitate the formation of coronary plaque in a monotonic fashion throughout the life course. We used genetic data from dbGAP (SEA, FHS, and MESA) as well as from the Stanford-Kaiser ADVANCE study imputed to the 1000 genomes project to examine the association between a genetic risk score (GRS) of high-risk alleles at these 49 SNPs and the presence of subclinical atherosclerosis. Subclinical atherosclerosis was identified by either pathologic examination of the coronary arteries or by radiographic assessment of coronary artery calcification (CAC). We stratified white/European subjects within each study into one of five age groups (≤30, 31-45, 46-60, 61-75, >75 years) and defined cases as subjects with either any raised lesions in their right coronary artery on autopsy (SEA, 26.7% subjects aged 18 to 30 years at time of unexpected death) or with an age and sex specific CAC score >75th percentile (all other studies, age > 30 years). Among 1561 cases and 5068 controls, we found a one SD increase in the GRS was associated with a 28% increased risk of having advanced subclinical coronary atherosclerosis (p = 3.82 x 10 -16 ). This increase in risk was significant in every age stratum (.01 > p > 9.4 x 10 -7 ) and was remarkably similar across all age strata (p test of heterogeneity = 0.99). We obtained near identical results and levels of significance when we restricted the GRS to 33 SNPs not associated with traditional risk factors. Our findings strongly support the notion that susceptibility alleles for clinical CAD uncovered through large-scale meta-analysis of GWAS uniformly promote the development of coronary atherosclerosis from birth. This predisposition is sustained at a constant level throughout one’s lifetime. Given it is observed at the earliest stage of plaque formation, it is unlikely to involve a concurrent predisposition to plaque rupture and/or thrombosis.

Sign in / Sign up

Export Citation Format

Share Document