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.

To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.

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.

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.

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.

There has been a relative dearth of epidemiological research into bipolar affective disorder. Furthermore, incidence studies of bipolar disorder have been predominantly retrospective and most only included hospital admission cases.

To determine the incidence of operationally defined bipolar disorder in three areas of the UK and to investigate any differences in gender and ethnicity.

All patients who contacted mental health services with first-episode psychosis or non-psychotic mania between September 1997 and August 1999 were identified and diagnosed according to ICD–10 criteria. Incidence rates of bipolar affective disorder were standardised for age and stratified by gender and ethnic group across the three areas.

The incidence rate per 100 000 per year in south-east London was over twice that in Nottingham and Bristol. There was no significant difference in the rates of disorder in men and women. Incidence rates of bipolar disorder in the combined Black and minority ethnic groups in all three areas were significantly higher than those of the comparison White groups.

The incidence of bipolar disorder was higher in south-east London than in the other two areas, and was higher among Black and minority ethnic groups than in the White population.