A saturated map of common genetic variants associated with human height

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes(1). Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel(2)) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants

The average consumer's degree of attention in trade mark cases -- in Landmark Cases of EU Consumer Law - In honour of Jules Stuyck

Cet article concerne la notion de consommateur moyen en droit des marques, critère d’appréciation-clé en droit des marques comme en droit de la consommation. Le « consommateur moyen » est un être abstrait, une fiction juridique, imaginé par la Cour de Justice de l’Union européenne, dont la jurisprudence n’est pas toujours ni très convaincante, ni très cohérente, comme le montre la présente contribution.info:eu-repo/semantics/publishe

High sensitivity C-reactive protein and cerebral white matter hyperintensities on magnetic resonance imaging in migraine patients

Migraine is a common headache disorder that may be associated with vascular disease and cerebral white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) scan. High sensitivity C-reactive protein (hs-CRP) is a marker of inflammation that may predict subclinical atherosclerosis. However, the relation between migraine, vascular risks, and WMHs is unknown. We evaluated hs-CRP levels and the relation between hs-CRP level and WMHs in adult migraine patients. This case-control study included 432 subjects (216 migraine patients [without aura, 143 patients; with aura, 73 patients]; 216 healthy control subjects without migraine; age range 18-50 y). Migraine diagnosis was determined according to the International Classification of Headache Disorders II diagnostic criteria. The migraine patients and control subjects had no known vascular risk factors, inflammatory disease, or comorbid disease. The presence and number of WMHs on MRI scans were determined, and serum hs-CRP levels were measured by latex-enhanced immunoturbidimetry. Mean hs-CRP level was significantly greater in migraine patients (1.94 +/- 2.03 mg/L) than control subjects (0.82 +/- 0.58 mg/L; P a parts per thousand currency signaEuro parts per thousand.0001). The mean number of WMHs per subject and the presence of WMHs was significantly greater in migraine patients (69 patients [31.9%]; 1.68 +/- 3.12 mg/dL) than control subjects (21 subjects [9.7%]; 0.3 +/- 1.3; P a parts per thousand currency signaEuro parts per thousand.001). However, there was no correlation between hs-CRP level and WMHs in migraine patients (r = 0.024; not significant). The presence of WMHs was increased 4.35-fold in migraine patients (odds ratio 4.35, P a parts per thousand currency signaEuro parts per thousand.001). High hs-CRP level may be a marker of the proinflammatory state in migraine patients. However, the absence of correlation between hs-CRP level and WMHs suggests that hs-CRP is not causally involved in the pathogenesis of WMHs in migraine patients. The WMHs were located mostly in the frontal lobe and subcortical area