scholarly journals Ten years of Enhancing Neuro-Imaging Genetics through Meta-Analysis: An overview from the ENIGMA Genetics Working Group

2020 ◽  
Author(s):  
Sarah Medland ◽  
Katrina L. Grasby ◽  
Neda Jahanshad ◽  
Jodie N. Painter ◽  
Lucía Colodro-Conde ◽  
...  
Keyword(s):  
Working Group ◽  
Neurological Diseases ◽  
Meta Analysis ◽  
Genetic Correlations ◽  
Brain Structures ◽  
Imaging Genetics ◽  
Association Analyses ◽  
Group A ◽  
Neuro Imaging ◽  
Neuroimaging Genetics

Here we review the motivation for creating the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium and the genetic analyses undertaken by the consortium so far. We discuss the methodological challenges, findings and future directions of the Genetics Working Group. A major goal of the working group is tackling the reproducibility crisis affecting ‘candidate gene’ and genome-wide association analyses in neuroimaging. To address this, we developed harmonised analytic methods, and support their use in coordinated analyses across sites worldwide, which also makes it possible to understand heterogeneity in results across sites. These efforts have resulted in the identification of hundreds of common genomic loci robustly associated with brain structure. We showed common and distinct genetic loci to be associated with different brain structures, as well as genetic correlations with psychiatric and neurological diseases.

scholarly journals Common Genetic Variation Indicates Separate Causes for Periventricular and Deep White Matter Hyperintensities

Stroke ◽  
2020 ◽  
Vol 51 (7) ◽  
pp. 2111-2121 ◽  
Author(s):  
Nicola J. Armstrong ◽  
Karen A. Mather ◽  
Muralidharan Sargurupremraj ◽  
Maria J. Knol ◽  
Rainer Malik ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Meta Analysis ◽  
Genetic Correlations ◽  
Imaging Genetics ◽  
Genome Wide Association ◽  
Association Analyses ◽  
New Genes ◽  
Genome Wide

Background and Purpose: Periventricular white matter hyperintensities (WMH; PVWMH) and deep WMH (DWMH) are regional classifications of WMH and reflect proposed differences in cause. In the first study, to date, we undertook genome-wide association analyses of DWMH and PVWMH to show that these phenotypes have different genetic underpinnings. Methods: Participants were aged 45 years and older, free of stroke and dementia. We conducted genome-wide association analyses of PVWMH and DWMH in 26,654 participants from CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology), ENIGMA (Enhancing Neuro-Imaging Genetics Through Meta-Analysis), and the UKB (UK Biobank). Regional correlations were investigated using the genome-wide association analyses -pairwise method. Cross-trait genetic correlations between PVWMH, DWMH, stroke, and dementia were estimated using LDSC. Results: In the discovery and replication analysis, for PVWMH only, we found associations on chromosomes 2 ( NBEAL ), 10q23.1 ( TSPAN14/FAM231A ), and 10q24.33 ( SH3PXD2A). In the much larger combined meta-analysis of all cohorts, we identified ten significant regions for PVWMH: chromosomes 2 (3 regions), 6, 7, 10 (2 regions), 13, 16, and 17q23.1. New loci of interest include 7q36.1 ( NOS3 ) and 16q24.2. In both the discovery/replication and combined analysis, we found genome-wide significant associations for the 17q25.1 locus for both DWMH and PVWMH. Using gene-based association analysis, 19 genes across all regions were identified for PVWMH only, including the new genes: CALCRL (2q32.1), KLHL24 (3q27.1), VCAN (5q27.1), and POLR2F (22q13.1). Thirteen genes in the 17q25.1 locus were significant for both phenotypes. More extensive genetic correlations were observed for PVWMH with small vessel ischemic stroke. There were no associations with dementia for either phenotype. Conclusions: Our study confirms these phenotypes have distinct and also shared genetic architectures. Genetic analyses indicated PVWMH was more associated with ischemic stroke whilst DWMH loci were implicated in vascular, astrocyte, and neuronal function. Our study confirms these phenotypes are distinct neuroimaging classifications and identifies new candidate genes associated with PVWMH only.

scholarly journals In vivo hippocampal subfield volumes in bipolar disorder—A mega‐analysis from The Enhancing Neuro Imaging Genetics through Meta‐Analysis Bipolar Disorder Working Group

2020 ◽  
Author(s):  
Unn K. Haukvik ◽  
Tiril P. Gurholt ◽  
Stener Nerland ◽  
Torbjørn Elvsåshagen ◽  
Theophilus N. Akudjedu ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Working Group ◽  
Meta Analysis ◽  
Imaging Genetics ◽  
Neuro Imaging

scholarly journals Ten years of enhancing neuro‐imaging genetics through meta‐analysis : An overview from the ENIGMA Genetics Working Group

2020 ◽  
Author(s):  
Sarah E. Medland ◽  
Katrina L. Grasby ◽  
Neda Jahanshad ◽  
Jodie N. Painter ◽  
Lucía Colodro‐Conde ◽  
...  
Keyword(s):  
Working Group ◽  
Meta Analysis ◽  
Imaging Genetics ◽  
Neuro Imaging

The ENIGMA Brain Injury Working Group: Approach, Challenges, and Potential Benefits

2019 ◽  
Author(s):  
Elisabeth A. Wilde ◽  
Emily L. Dennis ◽  
David F Tate
Keyword(s):  
Brain Injury ◽  
Working Group ◽  
Meta Analysis ◽  
Special Issue ◽  
Group Approach ◽  
Challenges And Opportunities ◽  
Brain Structure And Function ◽  
Potential Benefits ◽  
And Function ◽  
Neuroimaging Genetics

The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium brings together researchers from around the world to try to identify the genetic underpinnings of brain structure and function, along with robust, generalizable effects of neurological and psychiatric disorders. The recently-formed ENIGMA Brain Injury working group includes 8 subgroups, based largely on injury mechanism and patient population. This introduction to the special issue summarizes the history, organization, and objectives of ENIGMA Brain Injury, and includes a discussion of strategies, challenges, opportunities and goals common across 6 of the subgroups under the umbrella of ENIGMA Brain Injury. The following articles in this special issue, including 6 articles from different subgroups, will detail the challenges and opportunities specific to each subgroup.

scholarly journals Localizing genomic regions contributing to the extremes of externalizing behavior: ADHD, aggressive and antisocial behaviors

2019 ◽  
Author(s):  
Mariana L. Rodríguez-López ◽  
Hilleke Hulshoff Pol ◽  
Barbara Franke ◽  
Marieke Klein
Keyword(s):  
Externalizing Behavior ◽  
Meta Analysis ◽  
Neurodevelopmental Disorder ◽  
Expression Patterns ◽  
Genetic Correlations ◽  
Brain Regions ◽  
Genetic Loci ◽  
Association Analyses ◽  
Meta Analyses ◽  
Genomic Regions

AbstractAttention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder, which in some cases occurs comorbid with aggressive and antisocial behavior (AGG; ASB). The three externalizing behaviors are moderately to highly heritable and are genetically correlated. However, the genomic regions underlying this correlation are unknown. In this study, we aimed to localize genetic loci shared between ADHD, AGG, and ASB, using two complementary approaches.GWAS summary statistics for ADHD, AGG, and ASB were used for (1) cross-trait gene-based meta-analysis association analyses and (2) local genetic correlation analyses to identify shared genetic loci. Results of both complementary methods were combined to retrieve overlapping genes. Biological functionality of prioritized genes was assessed by exploring gene expression patterns in brain tissues and testing for gene-based association with (subcortical) brain regions.We confirmed previous findings that ADHD, AGG, and ASB were positively genetically correlated at a global level. We identified eleven significant genes in cross-trait gene-based meta-analyses, 31 loci shared between traits; 34 genes were identified when both approaches were combined.This study emphasizes the complex genetic architecture underlying global genetic correlations at the locus level. Converging evidence from these cross-trait analyses highlights novel candidate genes underlying biological mechanisms shared by ADHD, AGG, and ASB.

scholarly journals Acute sore throat and Fusobacterium necrophorum in primary healthcare: a systematic review and meta-analysis

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e042816
Author(s):  
Stefan Malmberg ◽  
Susanna Petrén ◽  
Ronny Gunnarsson ◽  
Katarina Hedin ◽  
Pär-Daniel Sundvall
Keyword(s):  
Systematic Review ◽  
Sore Throat ◽  
Primary Healthcare ◽  
Malignant Disease ◽  
Meta Analysis ◽  
Acute Infection ◽  
Fusobacterium Necrophorum ◽  
Secondary Outcome ◽  
Case Control Studies ◽  
Group A

PurposeThe main objective of this review was to describe and quantify the association between Fusobacterium necrophorum (FN) and acute sore throat in primary healthcare (PHC).MethodsIn this systematic review and meta-analysis, we searched Scopus and PubMed for case–control studies reporting the prevalence of FN in patients attending primary care for an uncomplicated acute sore throat as well as in healthy controls. Only studies published in English were considered. Publications were not included if they were case studies, or if they included patients prescribed antibiotics before the throat swab, patients with a concurrent malignant disease, on immunosuppression, having an HIV infection, or patients having another acute infection in addition to a sore throat. Inclusion criteria and methods were specified in advance and published in PROSPERO. The primary outcome was positive etiologic predictive value (P-EPV), quantifying the probability for an association between acute sore throat and findings of FN in the pharynx. For comparison, our secondary outcome was the corresponding P-EPV for group A Streptococcus (GAS).ResultsPubMed and Scopus yielded 258 and 232 studies, respectively. Removing duplicates and screening the abstracts resulted in 53 studies subsequently read in full text. For the four studies of medium to high quality included in the meta-analysis, the cumulative P-EPV regarding FN was 64% (95% CI 33% to 83%). GAS, based on data from the same publications and patients, yielded a positive EPV of 93% (95% CI 83% to 99%).ConclusionsThe results indicate that FN may play a role in PHC patients with an acute sore throat, but the association is much weaker compared with GAS.

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