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Background The effect of a healthy lifestyle on dementia associated with multimorbidity is not well understood. Our objective is to examine whether the adoption of a healthy lifestyle could potentially reduce the elevated risk of dementia in individuals with and without multimorbidity. Methods We utilized data from the UK Biobank cohort. A comprehensive healthy lifestyle score, ranging from 0 to 6, was generated. Cox proportional hazards models were used to examine the associations between multimorbidity, the healthy lifestyle score, and the incidence risk of dementia. Results Over a median follow-up period of 12.5 years, 5 852 all-cause dementia were recorded. Multimorbidity including cardiovascular, metabolic, neuropsychiatric, and inflammation-related diseases was associated with a higher risk of subsequent dementia. Each additional chronic disease was associated with a hazard ratio (HR) of 1.38 (95% CI: 1.33, 1.44). Compared to individuals without multimorbidity and a healthy lifestyle score of 5–6, patients with multimorbidity and a lifestyle score of 0–1 had a significantly higher risk of dementia (HR: 3.13; 95% CI: 2.64, 3.72), but the risk was markedly attenuated among those with multimorbidity and a lifestyle score of 5–6. Among patients with 3 or more diseases, the HR for dementia was 0.53 (95%CI: 0.42, 0.68) when comparing a lifestyle score of 5–6 to 0–1. And we observed more pronounced association between them among people younger than 60 years old. Conclusions Adherence to a combination of healthy lifestyle factors, especially at a young age, was associated with a significantly lower risk of dementia among participants with multimorbidity. [ABSTRACT FROM AUTHOR]

Sarcopenic obesity (SO) is an age-related disease characterized by the coexistence of excessive adiposity and low muscle mass or function. Although obesity and sarcopenia are heritable conditions, the genetic determinants of SO have not been fully understood. We conducted a large-scale exome-wide association analysis of SO in a sequenced sample of 2 887 cases and 113 284 controls and an imputed sample of 4 003 cases and 161 990 controls in the UK Biobank cohort. Single-variant association analysis identified one locus 1q41 (lead SNP rs1417066 , LYPLAL1-AS1 , odds ratio [OR] = 1.15, 95% confidence interval [CI] = [1.11–1.19], p  = 1.75 × 10−14) that was significantly associated with SO at the exome-wide significance level (p  < 1 × 10-8). Colocalization analysis in the Genotype-Tissue Expression expression quantitative trait locus database showed that LYPLAL1-AS1 was colocalized with SO in multiple musculoskeletal-related tissues. Gene-based burden test of rare loss-of-function variants identified 5 genes at the gene-wise significance level (p  < 4.3 × 10−6): PDE3B (OR = 2.48, p  = 1.10 × 10−6), MYOZ3 (OR = 25.49, p  = 1.41 × 10−7), SLC15A3 (OR = 4.75, p  = 6.82 × 10−7), RNF130 (OR = 25.83, p  = 4.07 × 10−6), and TNK2 (OR = 4.25, p  = 8.75 × 10−8). Overall, our study uncovered the genetic effects of both common and rare variants on SO susceptibility, expanded existing knowledge of the genetic architecture of SO, and improved understanding of the genetic mechanisms underlying SO. [ABSTRACT FROM AUTHOR]