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.

To evaluate long-term patterns of weight change and progression to overweight and obesity during adulthood.

Prospective study. Changes in mean BMI, waist circumference (WC) and weight were assessed over a mean 26-year follow-up (1971–1975 to 1998–2001). Mean BMI (95 % CI) and mean WC (95 % CI) of men and women in BMI and age groups were computed. Mean weight change in BMI and age categories was compared using analysis of covariance.

Framingham Heart Study Offspring/Spouse Nutrition Study.

Men and women (n 2394) aged 20–63 years.

During follow-up, increases in BMI (men: 2·2 kg/m2; women: 3·7 kg/m2) and WC (men: 5·7 cm; women: 15·1 cm) were larger in women than men. BMI gains were greatest in younger adults (20–39 years) and smallest in obese older adults (50–69 years). The prevalence of obesity doubled in men (to 33·2 %) and tripled in women (to 26·6 %). Among normal-weight individuals, abdominal obesity developed in women only. The prevalence of abdominal obesity increased 1·8-fold in men (to 53·0 %) and 2·4-fold in women (to 71·2 %). Weight gain was greatest in the youngest adults (20–29 years), particularly women. Gains continued into the fifth decade among men and then declined in the sixth decade; in women gains continued into the sixth decade.

Patterns of weight change and progression to obesity during adulthood differ in men and women. Preventive intervention strategies for overweight and obesity need to consider age- and sex-specific patterns of changes in anthropometric measures.