scholarly journals Alcohol Dependence Genetics: Lessons Learned From Genome-Wide Association Studies (GWAS) and Post-GWAS Analyses

2015 ◽  
Vol 39 (8) ◽  
pp. 1312-1327 ◽  
Author(s):  
Amy B. Hart ◽  
Henry R. Kranzler
Keyword(s):  
Alcohol Dependence ◽  
Association Studies ◽  
Lessons Learned ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

scholarly journals Cross-species alcohol dependence-associated gene networks: Co-analysis of mouse brain gene expression and human genome-wide association data

2018 ◽  
Author(s):  
Kristin M. Mignogna ◽  
Silviu A. Bacanu ◽  
Brien P. Riley ◽  
Aaron R. Wolen ◽  
Michael F. Miles
Keyword(s):  
Gene Expression ◽  
Alcohol Dependence ◽  
Mouse Brain ◽  
Gene Networks ◽  
Association Studies ◽  
Complex Trait ◽  
Genome Wide Association ◽  
Model Organisms ◽  
Genome Wide Association Studies ◽  
Genome Wide

AbstractGenome-wide association studies on alcohol dependence, by themselves, have yet to account for the estimated heritability of the disorder and provide incomplete mechanistic understanding of this complex trait. Integrating brain ethanol-responsive gene expression networks from model organisms with human genetic data on alcohol dependence could aid in identifying dependence-associated genes and functional networks in which they are involved. This study used a modification of the Edge-Weighted Dense Module Searching for genome-wide association studies (EW-dmGWAS) approach to co-analyze whole-genome gene expression data from ethanol-exposed mouse brain tissue, human protein-protein interaction databases and alcohol dependence-related genome-wide association studies. Results revealed novel ethanol-regulated and alcohol dependence-associated gene networks in prefrontal cortex, nucleus accumbens, and ventral tegmental area. Three of these networks were overrepresented with genome-wide association signals from an independent dataset. These networks were significantly overrepresented for gene ontology categories involving several mechanisms, including actin filament-based activity, transcript regulation, Wnt and Syndecan-mediated signaling, and ubiquitination. Together, these studies provide novel insight for brain mechanisms contributing to alcohol dependence.

scholarly journals Host genetics and microbiome associations from the lens of genome wide association studies

2018 ◽  
Author(s):  
Omer Weissbrod ◽  
Daphna Rothschild ◽  
Elad Barkan ◽  
Eran Segal
Keyword(s):  
Gut Microbiome ◽  
Complex Traits ◽  
Association Studies ◽  
Meta Analysis ◽  
Lessons Learned ◽  
Host Genome ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
History Of

Recent studies indicate that the gut microbiome is partially heritable, motivating the need to investigate microbiome-host genome associations via microbial genome-wide association studies (mGWAS). Existing mGWAS demonstrate that microbiome-host genotypes associations are typically weak and are spread across multiple variants, similar to associations often observed in genome-wide association studies (GWAS) of complex traits. Here we reconsider mGWAS by viewing them through the lens of GWAS, and demonstrate that there are striking similarities between the challenges and pitfalls faced by the two study designs. We further advocate the mGWAS community to adopt three key lessons learned over the history of GWAS: (a) Adopting uniform data and reporting formats to facilitate replication and meta-analysis efforts; (b) enforcing stringent statistical criteria to reduce the number of false positive findings; and (c) considering the microbiome and the host genome as distinct entities, rather than studying different taxa and single nucleotide polymorphism (SNPs) separately. Finally, we anticipate that mGWAS sample sizes will have to increase by orders of magnitude to reproducibly associate the host genome with the gut microbiome.

How to discover a metabolic pathway? An update on gene identification in aliphatic glucosinolate biosynthesis, regulation and transport

2014 ◽  
Vol 395 (5) ◽  
pp. 529-543 ◽  
Author(s):  
Lea Møller Jensen ◽  
Barbara Ann Halkier ◽  
Meike Burow
Keyword(s):  
Association Studies ◽  
Phylogenetic Analyses ◽  
Lessons Learned ◽  
Genome Wide Association ◽  
Gene Identification ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Aliphatic Glucosinolates ◽  
Biosynthesis Regulation

Abstract Identification of enzymes, regulators and transporters involved in different metabolic processes is the foundation to understand how organisms function. There are, however, many difficulties in identifying candidate genes as well as in proving their in vivo roles. In this review, we describe different approaches utilized in Arabidopsis thaliana to identify gene candidates and experiments required to prove the function of a given candidate. For example, we use the production of methionine-derived aliphatic glucosinolates that represent major defence compounds in A. thaliana. Nearly all biosynthetic genes, as well as the first sets of regulators and transporters, have been identified. An array of approaches, i.e. classical mapping, quantitative trait loci (QTL) mapping, eQTL mapping, co-expression, genome wide association studies (GWAS), mutant screens and phylogenetic analyses, has been exploited to increase the number of identified genes. Here we summarize the lessons learned from the different approaches used over the years with the aim to help designing and combining new approaches in the future.

A meta-analysis of two genome-wide association studies identifies 3 new loci for alcohol dependence

2011 ◽  
Vol 45 (11) ◽  
pp. 1419-1425 ◽  
Author(s):  
Ke-Sheng Wang ◽  
Xuefeng Liu ◽  
Qunyuan Zhang ◽  
Yue Pan ◽  
Nagesh Aragam ◽  
...  
Keyword(s):  
Alcohol Dependence ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

scholarly journals Pharmacogenomic genome-wide association studies: lessons learned thus far

2009 ◽  
Vol 10 (2) ◽  
pp. 161-163 ◽  
Author(s):  
James J Crowley ◽  
Patrick F Sullivan ◽  
Howard L McLeod
Keyword(s):  
Association Studies ◽  
Lessons Learned ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

scholarly journals On Genome-Wide Association Studies and Their Meta-Analyses: Lessons Learned From Osteoporosis Studies

2013 ◽  
Vol 98 (7) ◽  
pp. E1278-E1282 ◽  
Author(s):  
Yong-Jun Liu ◽  
Lei Zhang ◽  
Yufang Pei ◽  
Christopher J. Papasian ◽  
Hong-Wen Deng
Keyword(s):  
Association Studies ◽  
Lessons Learned ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Meta Analyses

scholarly journals Genome‐wide association studies of alcohol dependence, DSM‐IV criterion count and individual criteria

2019 ◽  
Author(s):  
Dongbing Lai ◽  
Leah Wetherill ◽  
Sarah Bertelsen ◽  
Caitlin E. Carey ◽  
Chella Kamarajan ◽  
...  
Keyword(s):  
Alcohol Dependence ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Dsm Iv
Sign in / Sign up

Export Citation Format

Share Document