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The present study aimed (1) to investigate how food cravings, sedentary behaviour (SB), and physical activity (PA) vary within and between individuals over time in a sample of high-trait food cravers and (2) to investigate within- and between-person associations of SB and PA with food craving (i.e. intensity and type of craved food) in high trait food cravers, thereby exploring the effects in different time intervals preceding the craving. An observational study with a repeated measures design was conducted in 95 high-trait food cravers (19-64 years), consisting of (1) 6-daily smartphone-based Ecological Momentary Assessment (EMA) questionnaires on food craving and (2) accelerometer data collection for 7 days. Analysis through generalised linear mixed models revealed the importance of focusing on individual fluctuations rather than between-person differences. Higher SB was linked to a lower likelihood of experiencing a craving and lower intensity of the cravings when they did occur. However, the relationship between SB and food cravings may be better explained by emotional, social, or contextual factors linked to the sitting episodes. Higher light physical activity (LPA) was associated with a higher intensity of food cravings indicating a potentially triggering effect. More moderate-to-vigorous physical activity (MVPA) was associated with a decreased likelihood of craving energy-dense foods, suggesting a protective role in unhealthy food choices. These associations varied across different timeframes. Despite the statistical significance of the findings, caution should be exercised when interpreting their practical implications, as they may not translate into substantial changes in everyday behaviour. Given the observational and exploratory nature of the analyses, the findings are intended to be hypothesis-generating rather than confirmatory, with the aim of informing future research. Show less

Global life expectancy has consistently increased since 1950, resulting in more people living to an older age. However, maintaining optimal cognitive health is a challenge as ageing is accompanied by natural cognitive decline, which can affect daily functioning and quality of life. Importantly, modifiable lifestyle factors can play a role in promoting healthy ageing. Among these, physical activity (PA), sedentary behaviour (SB) and sleep have gained increasing attention for their potential contributions to cognitive health. This study investigates in greater detail how these 24-hour movement behaviours relate to cognitive function in older adults. Participants were 233 healthy adults aged 55 years and older (51.1% women; mean age 68.3 ± 7.7 years). Daily time spent in light PA (LPA), moderate-to-vigorous PA (MVPA), SB and sleep was derived from 7-day wrist-worn ActiGraphy (wGT3X-BT). Cognitive function, including short-term and long-term memory (STM, LTM), executive function (EF) and processing speed, was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and expressed in z-scores. Compositional multiple linear regression was used to assess the association between time use and cognitive function. Compositional isotemporal substitution examined how hypothetical time reallocations between the different movement behaviours were related to cognitive function. Even after adjusting for age, sex, educational level, social isolation and multiple testing, time use was significantly associated with short-term memory (p = 0.01) and executive function (p = 0.001). Hypothetical time reallocations of 30-min from LPA to MVPA were associated with the largest significant mean differences of 0.19 [95% confidence interval 0.05-0.32] in STM z-scores and 0.21 [0.10-0.33] in EF z-scores. Notably, reallocating time from LPA or sleep to SB was also related to better EF z-scores. Importantly, reallocating even 5 minutes away from MVPA to any other behaviour was significantly associated with poorer z-scores in STM and EF. No significant associations were observed for long-term memory and processing speed. This study underscores the importance of considering 24-hour movement behaviours in cognitive health at older age. Dedicating time to moderate-to-vigorous PA seems to be important for specific cognitive domains. Longitudinal studies are needed to further explore these relationships, with a focus on detailed assessments of the various contexts in which PA and SB occur. Show less

Genetic studies might provide new insights into the biological mechanisms underlying lipid metabolism and risk of CAD. We therefore conducted a genome-wide association study to identify novel genetic determinants of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. We combined genome-wide association data from 8 studies, comprising up to 17 723 participants with information on circulating lipid concentrations. We did independent replication studies in up to 37 774 participants from 8 populations and also in a population of Indian Asian descent. We also assessed the association between single-nucleotide polymorphisms (SNPs) at lipid loci and risk of CAD in up to 9 633 cases and 38 684 controls. We identified 4 novel genetic loci that showed reproducible associations with lipids (probability values, 1.6×10(-8) to 3.1×10(-10)). These include a potentially functional SNP in the SLC39A8 gene for HDL-C, an SNP near the MYLIP/GMPR and PPP1R3B genes for LDL-C, and at the AFF1 gene for triglycerides. SNPs showing strong statistical association with 1 or more lipid traits at the CELSR2, APOB, APOE-C1-C4-C2 cluster, LPL, ZNF259-APOA5-A4-C3-A1 cluster and TRIB1 loci were also associated with CAD risk (probability values, 1.1×10(-3) to 1.2×10(-9)). We have identified 4 novel loci associated with circulating lipids. We also show that in addition to those that are largely associated with LDL-C, genetic loci mainly associated with circulating triglycerides and HDL-C are also associated with risk of CAD. These findings potentially provide new insights into the biological mechanisms underlying lipid metabolism and CAD risk. Show less

Plasma liver-enzyme tests are widely used in the clinic for the diagnosis of liver diseases and for monitoring the response to drug treatment. There is considerable evidence that human genetic variation influences plasma levels of liver enzymes. However, such genetic variation has not been systematically assessed. In the present study, we performed a genome-wide association study of plasma liver-enzyme levels in three populations (total n = 7715) with replication in three additional cohorts (total n = 4704). We identified two loci influencing plasma levels of alanine-aminotransferase (ALT) (CPN1-ERLIN1-CHUK on chromosome 10 and PNPLA3-SAMM50 on chromosome 22), one locus influencing gamma-glutamyl transferase (GGT) levels (HNF1A on chromosome 12), and three loci for alkaline phosphatase (ALP) levels (ALPL on chromosome 1, GPLD1 on chromosome 6, and JMJD1C-REEP3 on chromosome 10). In addition, we confirmed the associations between the GGT1 locus and GGT levels and between the ABO locus and ALP levels. None of the ALP-associated SNPs were associated with other liver tests, suggesting intestine and/or bone specificity. The mechanisms underlying the associations may involve cis- or trans-transcriptional effects (some of the identified variants were associated with mRNA transcription in human liver or lymphoblastoid cells), dysfunction of the encoded proteins (caused by missense variations at the functional domains), or other unknown pathways. These findings may help in the interpretation of liver-enzyme tests and provide candidate genes for liver diseases of viral, metabolic, autoimmune, or toxic origin. The specific associations with ALP levels may point to genes for bone or intestinal diseases. Show less