New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles

Genome-wide association analyses identify 123 susceptibility loci for migraine and implicate neurovascular mechanisms in its pathophysiology. Subtype analyses highlight risk loci specific for migraine with or without aura in addition to shared risk variants.Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.Clinical epidemiolog

Analysis of shared heritability in common disorders of the brain

Paroxysmal Cerebral Disorder

The ecology of the European badger (Meles meles) in Ireland: a review

peer-reviewedThe badger is an ecologically and economically important species. Detailed knowledge of aspects of the ecology of this animal in Ireland has only emerged through research over recent decades. Here, we review what is known about the species' Irish populations and compare these findings with populations in Britain and Europe. Like populations elsewhere, setts are preferentially constructed on south or southeast facing sloping ground in well-drained soil types. Unlike in Britain, Irish badger main setts are less complex and most commonly found in hedgerows. Badgers utilise many habitat types, but greater badger densities have been associated with landscapes with high proportions of pasture and broadleaf woodlands. Badgers in Ireland tend to have seasonally varied diets, with less dependence on earthworms than some other populations in northwest Europe. Recent research suggests that females exhibit later onset and timing of reproductive events, smaller litter sizes and lower loss of blastocysts than populations studied in Britain. Adult social groups in Ireland tend to be smaller than in Britain, though significantly larger than social groups from continental Europe. Although progress has been made in estimating the distribution and density of badger populations, national population estimates have varied widely in the Republic of Ireland. Future research should concentrate on filling gaps in our knowledge, including population models and predictive spatial modelling that will contribute to vaccine delivery, management and conservation strategies.Department of Agriculture, Fisheries and FoodTeagasc Walsh Fellowship Programm