Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus

Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (P(combined) = 4.09 × 10(-9); odds ratio (OR) = 1.21, 95% confidence interval (CI) =1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (P(combined) = 2.74 × 10(-10); OR = 1.14, 95% CI = 1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.

The Role of Variation at AβPP, PSEN1, PSEN2, and MAPT in Late Onset Alzheimer's Disease

Rare mutations in AßPP, PSEN1, and PSEN2 cause uncommon early onset forms of Alzheimer's disease (AD), and common variants in MAPT are associated with risk of other neurodegenerative disorders. We sought to establish whether common genetic variation in these genes confer risk to the common form of AD which occurs later in life (>65 years). We therefore tested single-nucleotide polymorphisms at these loci for association with late-onset AD (LOAD) in a large case-control sample consisting of 3,940 cases and 13,373 controls. Single-marker analysis did not identify any variants that reached genome-wide significance, a result which is supported by other recent genome-wide association studies. However, we did observe a significant association at the MAPT locus using a gene-wide approach (p = 0.009). We also observed suggestive association between AD and the marker rs9468, which defines the H1 haplotype, an extended haplotype that spans the MAPT gene and has previously been implicated in other neurodegenerative disorders including Parkinson's disease, progressive supranuclear palsy, and corticobasal degeneration. In summary common variants at AßPP, PSEN1, and PSEN2 and MAPT are unlikely to make strong contributions to susceptibility for LOAD. However, the gene-wide effect observed at MAPT indicates a possible contribution to disease risk which requires further study.

Genetic variants influencing human aging from late-onset Alzheimer's disease (LOAD) genome-wide association studies (GWAS)

Genetics plays a crucial role in human aging with up to 30% of those living to the mid-80s being determined by genetic variation. Survival to older ages likely entails an even greater genetic contribution. There is increasing evidence that genes implicated in age-related diseases, such as cancer and neuronal disease, play a role in affecting human life span. We have selected the 10 most promising late-onset Alzheimer's disease (LOAD) susceptibility genes identified through several recent large genome-wide association studies (GWAS). These 10 LOAD genes (APOE, CLU, PICALM, CR1, BIN1, ABCA7, MS4A6A, CD33, CD2AP, and EPHA1) have been tested for association with human aging in our dataset (1385 samples with documented age at death [AAD], age range: 58-108 years; mean age at death: 80.2) using the most significant single nucleotide polymorphisms (SNPs) found in the previous studies. Apart from the APOE locus (rs2075650) which showed compelling evidence of association with risk on human life span (p = 5.27 × 10(-4)), none of the other LOAD gene loci demonstrated significant evidence of association. In addition to examining the known LOAD genes, we carried out analyses using age at death as a quantitative trait. No genome-wide significant SNPs were discovered. Increasing sample size and statistical power will be imperative to detect genuine aging-associated variants in the future. In this report, we also discuss issues relating to the analysis of genome-wide association studies data from different centers and the bioinformatic approach required to distinguish spurious genome-wide significant signals from real SNP associations.

Romanticism and Blackwood's Magazine:'An Unprecedented Phenomenon'

Romanticism and Blackwood's Magazine is inspired by the ongoing critical fascination with Blackwood's Edinburgh Magazine, and the burgeoning recognition of its centrality to the Romantic age. Though the magazine itself was published continuously for well over a century and a half, this volume concentrates specifically on those years when William Blackwood was at the helm, beginning with his founding of the magazine in 1817 and closing with his death in 1834. These were the years when, as Samuel Taylor Coleridge put it in 1832, Blackwood's reigned as 'an unprecedented Phenomenon in the world of letters.' The magazine placed itself at the centre of the emerging mass media, commented decisively on all the major political and cultural issues that shaped the Romantic movement, and published some of the leading writers of the day, including Coleridge, Thomas De Quincey, John Galt, Felicia Hemans, James Hogg, Walter Scott, and Mary Shelley.

'This much-needed volume reminds us not only why Blackwood's was the most influential periodical publication of the time, but also how its writers, writings, and critical agendas continue to shape so many of the scholarly concerns of Romantic studies in the twenty-first century.' - Charles Mahoney, Associate Professor, University of Connecticut, USA

List of Illustrations
Acknowledgements
Abbreviations
Notes on Contributors
'A character so various, and yet so indisputably its own': A Passage to Blackwood's Edinburgh Magazine; R.Morrison & D.S.Roberts
PART I: BLACKWOOD'S AND THE PERIODICAL PRESS
Beginning Blackwood's: The Right Mix of Dulce and Ùtile; P.Flynn
John Gibson Lockhart and Blackwood's: Shaping the Romantic Periodical Press; T.Richardson
From Gluttony to Justified Sinning: Confessional Writing in Blackwood's and the London Magazine; D.Higgins
Camaraderie and Conflict: De Quincey and Wilson on Enemy Lines; R.Morrison
Selling Blackwood's Magazine, 1817-1834; D.Finkelstein
PART II: BLACKWOOD'S CULTURE AND CRITICISM
Blackwood's 'Personalities'; T.Mole
Communal Reception, Mary Shelley, and the 'Blackwood's School' of Criticism; N.Mason
Blackwoodian Allusion and the Culture of Miscellaneity; D.Stewart
Blackwood's Edinburgh Magazine in the Scientific Culture of Early Nineteenth-Century Edinburgh; W.Christie
The Art and Science of Politics in Blackwood's Edinburgh Magazine, c. 1817-1841; D.Kelly
Prosing Poetry: Blackwood's and Generic Transposition, 1820-1840; J.Camlot
PART III: BLACKWOOD'S FICTIONS
Blackwood's and the Boundaries of the Short Story; T.Killick
The Edinburgh of Blackwood's Edinburgh Magazine and James Hogg's Fiction; G.Hughes
'The Taste for Violence in Blackwood's Magazine'; M.Schoenfield
PART IV: BLACKWOOD'S AT HOME
John Wilson and Regency Authorship; R.Cronin
John Wilson and Sport; J.Strachan
William Maginn and the Blackwood's 'Preface' of 1826; D.E.Latané, Jr.
All Work and All Play: Felicia Hemans's Edinburgh Noctes; N.Sweet
PART V: BLACKWOOD'S ABROAD
Imagining India in Early Blackwood's; D.S.Roberts
Tales of the Colonies: Blackwood's, Provincialism, and British Interests Abroad; A.Jarrells
Selected Bibliography
Index

ROBERT MORRISON is Queen's National Scholar at Queen's University, Kingston, Ontario, Canada. His book, The English Opium-Eater: A Biography of Thomas De Quincey was a finalist for the James Tait Black Prize. He has edited writings by Jane Austen, Leigh Hunt, Thomas De Quincey, and John Polidori.
DANIEL SANJIV ROBERTS is Reader in English at Queen's University Belfast, UK. His publications include a monograph, Revisionary Gleam: De Quincey, Coleridge, and the High Romantic Argument (2000), and major critical editions of Thomas De Quincey's Autobiographic Sketches and Robert Southey's The Curse of Kehama; the latter was cited as a Distinguished Scholarly Edition by the MLA. He is currently working on an edition of Charles Johnstone's novel The History of Arsaces, Prince of Betlis for the Early Irish Fiction series.

Seven new loci associated with age-related macular degeneration

Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate the understanding of AMD biology and help design new therapies, we executed a collaborative genome-wide association study, including >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 loci associated at P <5 × 10(-8). These loci show enrichment for genes involved in the regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include seven loci with associations reaching P <5 × 10(-8) for the first time, near the genes COL8A1-FILIP1L, IER3-DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9 and B3GALTL. A genetic risk score combining SNP genotypes from all loci showed similar ability to distinguish cases and controls in all samples examined. Our findings provide new directions for biological, genetic and therapeutic studies of AMD.