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Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
A masterpiece of rhetoric and an impassioned defence of faith in the face of persecution, this work represents a key work in the Latin patristic canon. Addressing the magistrates of the Roman court, Tertullian submits 'the real facts in the case of the Christians', defending the legitimacy of the new faith while charging its detractors with hypocrisy and worse. Scathing, eloquent and defiant, the Apology demonstrates the importance of classical rhetoric to the identity of the controversial religion and its recent converts. This edition (1917), accompanied by a complete commentary by J. E. B. Mayor and translation by Alexander Souter, has been called 'by the far the best commentary ever published' on the work. Published posthumously from Mayor's extensive Cambridge lecture notes, the commentary is a starting point for anyone seeking a full understanding of the text's critical history. Souter's English translation makes it accessible to experts and non-experts alike.
Richard of Cirencester (c.1335–1400) wrote his Latin history of the deeds of the English kings while he was a Benedictine monk at St Peter's, Westminster. His work is largely unoriginal and derivative of other historians, but it does contain valuable information about Westminster Abbey, as well as a full account of the saints whose tombs were to be seen in the abbey church. The fourth (and last) book concentrates solely on the reign and deeds of Edward the Confessor. Although Richard expresses an intention to continue his story in a fifth book, beginning with William the Conqueror, there is no evidence that he ever did so. This second volume, published in 1869, includes a lengthy preface by editor John Eyton Bickersteth Mayor (1825–1910) in which he discusses the work De situ Britanniae, once attributed to Richard, and establishes that it is in fact an eighteenth-century forgery.
Richard of Cirencester (c.1335–1400) wrote his Latin history of the deeds of the English kings while he was a Benedictine monk at St Peter's, Westminster. His work is largely unoriginal and derivative of other historians, but it does contain valuable information about Westminster Abbey, as well as a full account of the saints whose tombs were to be seen in the abbey church. The fourth (and last) book concentrates solely on the reign and deeds of Edward the Confessor. Although Richard expresses an intention to continue his story in a fifth book, beginning with William the Conqueror, there is no evidence that he ever did so. This first volume of a two-volume work, edited by the scholar John Eyton Bickersteth Mayor (1825–1910) and published in 1863, covers the period from the legendary accession of Vortigern in 447 up to the death of Ethelred of Wessex in 871.
The second edition of John Mayor's 1853 commentary on the Roman satirist Juvenal was published in the years 1872 to 1879, and according to the author's preface was intended as a precursor to an even larger-scale study. Thirteen of Juvenal's satires are featured here (Satires 2, 6 and 9 are omitted) and a thorough commentary is given for each, guiding the reader through the poet's intricate language and a dense web of historical and mythological allusions. Mayor (1825–1910), who was elected Professor of Latin at Cambridge in 1872 and became one of the original Fellows of the British Academy, applied his extensive knowledge of thought and life in Imperial Rome to make this difficult material more approachable. Volume 2 contains Mayor's notes on Satires 8 and 10–16.
The second edition of John Mayor's 1853 commentary on the Roman satirist Juvenal was published in the years 1872 to 1879, and according to the author's preface was intended as a precursor to an even larger-scale study. Thirteen of Juvenal's satires are featured here (Satires 2, 6 and 9 are omitted) and a thorough commentary is given for each, guiding the reader through the poet's intricate language and a dense web of historical and mythological allusions. Mayor (1825–1910), who was elected Professor of Latin at Cambridge in 1872 and became one of the original Fellows of the British Academy, applied his extensive knowledge of thought and life in Imperial Rome to make this difficult material more approachable. Volume 1 contains the text of the satires, and Mayor's notes on the first five pieces in his selection.