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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.
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.
Although garlic and onions have long been associated with putative cardiovascular health benefits, the effects of different commercially available onions and level of intake have not been studied. Therefore, the aim of the present study was to evaluate the potential health benefits of raw onions using the pig as a biomedical model. Twenty-five female (Large White×Landrace) pigs were used in a (2×2)+1 factorial experiment. Pigs were fed a standard grower diet supplemented with 100 g tallow/kg with the addition of Allium cepa var. cavalier or var. destiny at 0, 10 or 25 g/MJ digestible energy for 6 weeks. Overall, the consumption of onions resulted in significant reductions in plasma triacylglycerol; however, the reductions were most pronounced in pigs fed destiny onions (−26 %, P=0·042). Total plasma cholesterol and LDL:HDL ratios were not significantly different. Onion supplementation, regardless of the variety, resulted in dose-dependent reductions in erythrocyte counts and Hb levels, while the white blood cell concentrations, particularly lymphocytes, were increased in pigs that consumed onions. Furthermore, indices of blood clotting were largely unaffected by onion consumption. In conclusion, dietary supplementation with raw brown onions has moderate lipid-modulating and immunostimulatory properties. However, daily onion intake >25 g/MJ digestible energy could be detrimental to erythrocyte numbers.
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