scholarly journals Genome-wide association studies suggest limited immune gene enrichment in schizophrenia compared to five autoimmune diseases

2015 ◽  
Author(s):  
Jennie G. Pouget ◽  
Vanessa F. Gonçalves ◽  
Sarah L. Spain ◽  
Hilary K. Finucane ◽  
Soumya Raychaudhuri ◽  
...  
Keyword(s):  
Association Studies ◽  
Genome Wide Association ◽  
Future Research ◽  
Immune Gene ◽  
Genome Wide Association Studies ◽  
Immune Genes ◽  
Genome Wide ◽  
Immune Alterations ◽  
Pathway Analyses ◽  
Immune Loci

AbstractThere has been intense debate over the immunological basis of schizophrenia, and the potential utility of adjunct immunotherapies. The major histocompatibility complex is consistently the most powerful region of association in genome-wide association studies (GWASs) of schizophrenia, and has been interpreted as strong genetic evidence supporting the immune hypothesis. However, global pathway analyses provide inconsistent evidence of immune involvement in schizophrenia, and it remains unclear whether genetic data support an immune etiology per se. Here we empirically test the hypothesis that variation in immune genes contributes to schizophrenia. We show that there is no enrichment of immune loci outside of the MHC region in the largest genetic study of schizophrenia conducted to date, in contrast to five diseases of known immune origin. Among 108 regions of the genome previously associated with schizophrenia, we identify six immune candidates (DPP4, HSPD1, EGR1, CLU, ESAM, NFATC3) encoding proteins with alternative, nonimmune roles in the brain. While our findings do not refute evidence that has accumulated in support of the immune hypothesis, they suggest that genetically mediated alterations in immune function may not play a major role in schizophrenia susceptibility. Instead, there may be a role for pleiotropic effects of a small number of immune genes that also regulate brain development and plasticity. Whether immune alterations drive schizophrenia progression is an important question to be addressed by future research, especially in light of the growing interest in applying immunotherapies in schizophrenia.

scholarly journals Genome-Wide Association Studies Suggest Limited Immune Gene Enrichment in Schizophrenia Compared to 5 Autoimmune Diseases

2016 ◽  
Vol 42 (5) ◽  
pp. 1176-1184 ◽  
Author(s):  
Jennie G. Pouget ◽  
Vanessa F. Gonçalves ◽  
Sarah L. Spain ◽  
Hilary K. Finucane ◽  
Soumya Raychaudhuri ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Association Studies ◽  
Genome Wide Association ◽  
Immune Gene ◽  
Genome Wide Association Studies ◽  
Gene Enrichment ◽  
Genome Wide

scholarly journals Invited review: Genome-wide association analysis for quantitative traits in livestock – a selective review of statistical models and experimental designs

2017 ◽  
Vol 60 (3) ◽  
pp. 335-346 ◽  
Author(s):  
Markus Schmid ◽  
Jörn Bennewitz
Keyword(s):  
Statistical Models ◽  
Complex Traits ◽  
Quantitative Traits ◽  
Association Studies ◽  
Real Data ◽  
Genome Wide Association ◽  
Future Research ◽  
Genome Wide Association Studies ◽  
Livestock Breeding ◽  
Genome Wide

Abstract. Quantitative or complex traits are controlled by many genes and environmental factors. Most traits in livestock breeding are quantitative traits. Mapping genes and causative mutations generating the genetic variance of these traits is still a very active area of research in livestock genetics. Since genome-wide and dense SNP panels are available for most livestock species, genome-wide association studies (GWASs) have become the method of choice in mapping experiments. Different statistical models are used for GWASs. We will review the frequently used single-marker models and additionally describe Bayesian multi-marker models. The importance of nonadditive genetic and genotype-by-environment effects along with GWAS methods to detect them will be briefly discussed. Different mapping populations are used and will also be reviewed. Whenever possible, our own real-data examples are included to illustrate the reviewed methods and designs. Future research directions including post-GWAS strategies are outlined.

scholarly journals Genome-Wide Association Analyses of Fertility Traits in Beef Heifers

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 217
Author(s):  
Morgan R. Stegemiller ◽  
Gordon K. Murdoch ◽  
Troy N. Rowan ◽  
Kimberly M. Davenport ◽  
Gabrielle M. Becker ◽  
...  
Keyword(s):  
Mixed Model ◽  
Association Studies ◽  
Principal Component ◽  
Genome Wide Association ◽  
Trend Test ◽  
Future Research ◽  
Genome Wide Association Studies ◽  
Chromosome 2 ◽  
Beef Heifers ◽  
Genome Wide

The ability of livestock to reproduce efficiently is critical to the sustainability of animal agriculture. Antral follicle count (AFC) and reproductive tract scores (RTS) can be used to estimate fertility in beef heifers, but the genetic mechanisms influencing variation in these measures are not well understood. Two genome-wide association studies (GWAS) were conducted to identify the significant loci associated with these traits. In total, 293 crossbred beef heifers were genotyped on the Bovine GGP 50K chip and genotypes were imputed to 836,121 markers. A GWAS was performed with the AFC phenotype for 217 heifers with a multi-locus mixed model, conducted using the year, age at time of sampling and principal component analysis groupings as the covariates. The RTS GWAS was performed with 289 heifers using an additive correlation/trend test comparing prepubertal to pubertal heifers. The loci on chromosomes 2, 3 and 23 were significant in the AFC GWAS and the loci on chromosomes 2, 8, 10 and 11 were significant in the RTS GWAS. The significant region on chromosome 2 was similar between both analyses. These regions contained genes associated with cell proliferation, transcription, apoptosis and development. This study proposes candidate genes for beef cattle fertility, although future research is needed to elucidate the precise mechanisms.

scholarly journals Genome-wide Association Study Links APOEɛ4 and BACE1 Variants with Plasma Amyloid β Levels

2017 ◽  
Author(s):  
Vincent Chouraki ◽  
Sven J van der Lee ◽  
Benjamin Grenier-Boley ◽  
Jeannette Simino ◽  
Hieab Adams ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Association Studies ◽  
Phase 1 ◽  
Amyloid Β ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Chromosome 11 ◽  
Genome Wide ◽  
App Metabolism ◽  
Pathway Analyses

AbstractBackgroundAmyloid β (Aβ) peptides are the products of the catalytic processing of the Aβ precursor protein (APP) by the β-secretase, BACE1 and the γ-secretase complex. Impairment of the Aβ production/clearance balance is the major pathophysiological hypothesis in Alzheimer’s disease (AD). Plasma Aβ levels are easy to measure in large numbers and therefore can be used as an endophenotype to study the genetics of Aβ and its relevance to AD.MethodsWe performed genome-wide association studies (GWAS) of plasma Aβ1-40, Aβ1-42 and Aβ1-42/Aβ1-40 ratio in 12,369 non-demented participants across 8 studies, using genetic data imputed on the 1000 Genomes phase 1 version 3 reference panel. To gain further insight, we performed LD-score regression analysis of plasma Aβ-42 and Aβ-40 levels using previously published GWAS of AD and other related traits, and pathway analyses.ResultsWe identified 21 variants reaching genome-wide significance across two loci. The most significant locus spanned the APOE gene, with significant associations with plasma Aβ42 levels (p = 9.01×10-13) and plasma Aβ42/Aβ40 ratio (p = 6.46×10-20). The second locus was located on chromosome 11, near the BACE1 gene (p = 2.56×10-8). We also observed suggestive evidence of association (p < 1×10-5) around genes involved in Aβ metabolism including APP and PSEN2.ConclusionUsing plasma Aβ40 and Aβ42 levels, this GWAS was able to identify relevant and central actors of the APP metabolism in AD. Overall, this study strengthens the utility of plasma Aβ levels both as an endophenotype and a biomarker.

Sign in / Sign up

Export Citation Format

Share Document