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University College Cork
IE
4 researchers0 verified4 linked papers4,722 indexed citations
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2022 · Nature · 2,848 citations
Mapping genomic loci implicates genes and synaptic biology in schizophrenia
Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies. A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.
2021 · Neuroscience & Biobehavioral Reviews · 1,494 citations
The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder
BACKGROUND: Misconceptions about ADHD stigmatize affected people, reduce credibility of providers, and prevent/delay treatment. To challenge misconceptions, we curated findings with strong evidence base. METHODS: We reviewed studies with more than 2000 participants or meta-analyses from five or more studies or 2000 or more participants. We excluded meta-analyses that did not assess publication bias, except for meta-analyses of prevalence. For network meta-analyses we required comparison adjusted funnel plots. We excluded treatment studies with waiting-list or treatment as usual controls. From this literature, we extracted evidence-based assertions about the disorder. RESULTS: We generated 208 empirically supported statements about ADHD. The status of the included statements as empirically supported is approved by 80 authors from 27 countries and 6 continents. The contents of the manuscript are endorsed by 366 people who have read this document and agree with its contents. CONCLUSIONS: Many findings in ADHD are supported by meta-analysis. These allow for firm statements about the nature, course, outcome causes, and treatments for disorders that are useful for reducing misconceptions and stigma.
2020 · Nutrition Research Reviews · 286 citations
The biology of ergothioneine, an antioxidant nutraceutical
Ergothioneine (ERG) is an unusual thio-histidine betaine amino acid that has potent antioxidant activities. It is synthesised by a variety of microbes, especially fungi (including in mushroom fruiting bodies) and actinobacteria, but is not synthesised by plants and animals who acquire it via the soil and their diet, respectively. Animals have evolved a highly selective transporter for it, known as solute carrier family 22, member 4 (SLC22A4) in humans, signifying its importance, and ERG may even have the status of a vitamin. ERG accumulates differentially in various tissues, according to their expression of SLC22A4, favouring those such as erythrocytes that may be subject to oxidative stress. Mushroom or ERG consumption seems to provide significant prevention against oxidative stress in a large variety of systems. ERG seems to have strong cytoprotective status, and its concentration is lowered in a number of chronic inflammatory diseases. It has been passed as safe by regulatory agencies, and may have value as a nutraceutical and antioxidant more generally.
2019 · Current Opinion in Allergy and Clinical Immunology · 94 citations
Microbiome and skin biology
PURPOSE OF REVIEW: The skin is home to a diverse milieu of bacteria, fungi, viruses, bacteriophages, and archaeal communities. The application of culture-independent approaches has revolutionized the characterization of the skin microbiome and have revealed a previously underappreciated phylogenetic and functional granularity of skin-associated microbes in both health and disease states. RECENT FINDINGS: The physiology of a given skin-niche drives the site-specific differences in bacterial phyla composition of healthy skin. Changes in the skin microbiome have consistently been associated with atopic dermatitis. In particular, Staphylococcus aureus overgrowth with concomitant decline in Staphylococcus epidermidis is a general feature associated with atopic dermatitis and is not restricted to eczematous lesions. Changes in fungal species are now also being described. Changes in the composition and metabolic activity of the gut microbiota are associated with skin health. SUMMARY: We are now beginning to appreciate the intimate and intricate interactions between microbes and skin health. Multiple studies are currently focused on the manipulation of the skin or gut microbiome to explore their therapeutic potential in the prevention and treatment of skin inflammation.