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"Strachan, Mari"
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It never occurred to me that my writing was worthy of publication
By the time she was an adult she says she lacked time as well as confidence to write a book or seek a publisher. When pressed Mari admits her children were 'quite excited' by her success and one of her grandchildren, who she credits at the front of her first novel, was excited to see his name alongside so many languages.
Newspaper Article
Dead man's embers
In the aftermath of the Great War, Non Davies wakes one morning to find her husband crouching under the kitchen table in a cold sweat and with fear in his eyes, shouldering an imaginary rifle. During the intense heat of that summer she forces herself to sit and watch him, knowing she has to discover what has changed her Davey so completely.
Book
Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine
Aarno Palotie and colleagues present results of a large genome-wide association study of migraine. They identified significant associations at 38 distinct loci and found enrichment for genes expressed in vascular and smooth muscle tissues.
Migraine is a debilitating neurological disorder affecting around one in seven people worldwide, but its molecular mechanisms remain poorly understood. There is some debate about whether migraine is a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association (GWA) studies have thus far identified 13 independent loci associated with migraine. To identify new susceptibility loci, we carried out a genetic study of migraine on 59,674 affected subjects and 316,078 controls from 22 GWA studies. We identified 44 independent single-nucleotide polymorphisms (SNPs) significantly associated with migraine risk (
P
< 5 × 10
−8
) that mapped to 38 distinct genomic loci, including 28 loci not previously reported and a locus that to our knowledge is the first to be identified on chromosome X. In subsequent computational analyses, the identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, consistent with a predominant theory of migraine that highlights vascular etiologies.
Journal Article
Genome-wide meta-analysis identifies new susceptibility loci for migraine
Verneri Anttila and colleagues report meta-analysis of 29 genome-wide association studies for migraine. They identify five loci newly associated with migraine, three of which are associated with specific subtypes of migraine with or without aura.
Migraine is the most common brain disorder, affecting approximately 14% of the adult population, but its molecular mechanisms are poorly understood. We report the results of a meta-analysis across 29 genome-wide association studies, including a total of 23,285 individuals with migraine (cases) and 95,425 population-matched controls. We identified 12 loci associated with migraine susceptibility (
P
< 5 × 10
−8
). Five loci are new: near
AJAP1
at 1p36, near
TSPAN2
at 1p13, within
FHL5
at 6q16, within
C7orf10
at 7p14 and near
MMP16
at 8q21. Three of these loci were identified in disease subgroup analyses. Brain tissue expression quantitative trait locus analysis suggests potential functional candidate genes at four loci:
APOA1BP
,
TBC1D7
,
FUT9
,
STAT6
and
ATP5B
.
Journal Article
European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation
Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities.
The genetic basis of atopic dermatitis is not fully understood. Here, the authors find 91 genetic loci associated with atopic dermatitis in a GWAS of >1million individuals, which highlight the importance of systemic immune regulation.
Journal Article
The role of turbulence in coronal heating and solar wind expansion
Plasma in the Sun's hot corona expands into the heliosphere as a supersonic and highly magnetized solar wind. This paper provides an overview of our current understanding of how the corona is heated and how the solar wind is accelerated. Recent models of magnetohydrodynamic turbulence have progressed to the point of successfully predicting many observed properties of this complex, multi-scale system. However, it is not clear whether the heating in open-field regions comes mainly from the dissipation of turbulent fluctuations that are launched from the solar surface, or whether the chaotic 'magnetic carpet' in the low corona energizes the system via magnetic reconnection. To help pin down the physics, we also review some key observational results from ultraviolet spectroscopy of the collisionless outer corona.
Journal Article
A genome-wide cross-phenotype meta-analysis of the association of blood pressure with migraine
Blood pressure (BP) was inconsistently associated with migraine and the mechanisms of BP-lowering medications in migraine prophylaxis are unknown. Leveraging large-scale summary statistics for migraine (
N
cases
/
N
controls
= 59,674/316,078) and BP (
N
= 757,601), we find positive genetic correlations of migraine with diastolic BP (DBP,
r
g
= 0.11,
P
= 3.56 × 10
−06
) and systolic BP (SBP,
r
g
= 0.06,
P
= 0.01), but not pulse pressure (PP,
r
g
= −0.01,
P
= 0.75). Cross-trait meta-analysis reveals 14 shared loci (
P
≤ 5 × 10
−08
), nine of which replicate (
P
< 0.05) in the UK Biobank. Five shared loci (
ITGB5
,
SMG6
,
ADRA2B
,
ANKDD1B
, and
KIAA0040
) are reinforced in gene-level analysis and highlight potential mechanisms involving vascular development, endothelial function and calcium homeostasis. Mendelian randomization reveals stronger instrumental estimates of DBP (OR [95% CI] = 1.20 [1.15–1.25]/10 mmHg;
P
= 5.57 × 10
−25
) on migraine than SBP (1.05 [1.03–1.07]/10 mmHg;
P
= 2.60 × 10
−07
) and a corresponding opposite effect for PP (0.92 [0.88–0.95]/10 mmHg;
P
= 3.65 × 10
−07
). These findings support a critical role of DBP in migraine susceptibility and shared biology underlying BP and migraine.
The association between blood pressure (BP) and migraine is poorly understood. Here, the authors explore this relationship using summary-level GWAS data for BP and migraine. Cross-trait meta-analysis reveals shared loci between BP and migraine, while Mendelian randomization suggests that diastolic BP specifically plays a key role in migraine susceptibility.
Journal Article
Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
Ken Ong and colleagues report meta-analysis of 32 genome-wide association studies for age at menarche. They identify 30 loci newly associated with age at menarche, including four that were previously associated with BMI.
To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at
LIN28B
(
P
= 5.4 × 10
−60
) and 9q31.2 (
P
= 2.2 × 10
−33
), we identified 30 new menarche loci (all
P
< 5 × 10
−8
) and found suggestive evidence for a further 10 loci (
P
< 1.9 × 10
−6
). The new loci included four previously associated with body mass index (in or near
FTO
,
SEC16B
,
TRA2B
and
TMEM18
), three in or near other genes implicated in energy homeostasis (
BSX
,
CRTC1
and
MCHR2
) and three in or near genes implicated in hormonal regulation (
INHBA
,
PCSK2
and
RXRG
). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.
Journal Article
Molecular genetic overlap between migraine and major depressive disorder
Migraine and major depressive disorder (MDD) are common brain disorders that frequently co-occur. Despite epidemiological evidence that migraine and MDD share a genetic basis, their overlap at the molecular genetic level has not been thoroughly investigated. Using single-nucleotide polymorphism (SNP) and gene-based analysis of genome-wide association study (GWAS) genotype data, we found significant genetic overlap across the two disorders. LD Score regression revealed a significant SNP-based heritability for both migraine (h2 = 12%) and MDD (h2 = 19%), and a significant cross-disorder genetic correlation (rG = 0.25; P = 0.04). Meta-analysis of results for 8,045,569 SNPs from a migraine GWAS (comprising 30,465 migraine cases and 143,147 control samples) and the top 10,000 SNPs from a MDD GWAS (comprising 75,607 MDD cases and 231,747 healthy controls), implicated three SNPs (rs146377178, rs672931, and rs11858956) with novel genome-wide significant association (PSNP ≤ 5 × 10−8) to migraine and MDD. Moreover, gene-based association analyses revealed significant enrichment of genes nominally associated (Pgene-based ≤ 0.05) with both migraine and MDD (Pbinomial-test = 0.001). Combining results across migraine and MDD, two genes, ANKDD1B and KCNK5, produced Fisher’s combined gene-based P values that surpassed the genome-wide significance threshold (PFisher’s-combined ≤ 3.6 × 10−6). Pathway analysis of genes with PFisher’s-combined ≤ 1 × 10−3 suggested several pathways, foremost neural-related pathways of signalling and ion channel regulation, to be involved in migraine and MDD aetiology. In conclusion, our study provides strong molecular genetic support for shared genetically determined biological mechanisms underlying migraine and MDD.
Journal Article