The genetic architecture of the human hypothalamus and its involvement in neuropsychiatric behaviours and disorders.

Despite its crucial role in the regulation of vital metabolic and neurological functions, the genetic architecture of the hypothalamus remains unknown. Here we conducted multivariate genome-wide association studies (GWAS) using hypothalamic imaging data from 32,956 individuals to uncover the genetic underpinnings of the hypothalamus and its involvement in neuropsychiatric traits. There were 23 significant loci associated with the whole hypothalamus and its subunits, with functional enrichment for genes involved in intracellular trafficking systems and metabolic processes of steroid-related compounds. The hypothalamus exhibited substantial genetic associations with limbic system structures and neuropsychiatric traits including chronotype, risky behaviour, cognition, satiety and sympathetic-parasympathetic activity. The strongest signal in the primary GWAS, the ADAMTS8 locus, was replicated in three independent datasets (N = 1,685-4,321) and was strengthened after meta-analysis. Exome-wide association analyses added evidence to the association for ADAMTS8, and Mendelian randomization showed lower ADAMTS8 expression with larger hypothalamic volumes. The current study advances our understanding of complex structure-function relationships of the hypothalamus and provides insights into the molecular mechanisms that underlie hypothalamic formation.

Tea consumption and risk of incident dementia: A prospective cohort study of 377 592 UK Biobank participants.

As a widely consumed beverage, tea boasts diverse health benefits. Herein, we aimed to investigate the association between tea consumption and dementia risk. We conducted a prospective cohort study with 377 592 UK Biobank participants during a 9-year follow-up. Cox regression models adjusted for age, sex, ethnicity, Townsend deprivation index, education, body mass index, lifestyle factors, dietary factors and apolipoprotein E4 status were used to examine the association of tea consumption with dementia risk. Subgroup analyses stratified by age, sex and forms of dementia (Alzheimer's disease [AD] and vascular dementia [VD]) were performed. Moreover, the restricted cubic splines were used to calculate the nonlinear relationship between daily dosage of tea and dementia risk. After adjustment for all covariates, tea drinkers were 16% (95% confidence interval: 8-23) less likely to develop dementia compared with non-drinkers. Moderate consumption (1-6 cups/day) of tea exerted significant protective effects. Subgroup analyses showed that mid-aged participants or males benefited more from tea consumption. Moreover, moderate drinkers had a 16-19% lower hazard of AD and a 25-29% lower hazard of VD. Furthermore, a U-shaped association between tea consumption and dementia risk was shown (Pnon-linearity = 7E-04), and the consumption of around three cups per day showed the strongest protective effect. Within 3 cups/day, drinking one extra cup of tea per day brought a 6% reduction of incidence. In conclusion, moderate consumption of tea was significantly associated with a reduced risk of dementia, suggesting that tea consumption could be a modifiable lifestyle factor for dementia.