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Background Genetic evidence implicates the DISC1 gene in the etiology of a number of mental illnesses. Previously, we have reported association between DISC1 and measures of psychosis proneness, the Revised Social Anhedonia Scale (RSAS) and Revised Physical Anhedonia Scale (RPAS), in the Northern Finland Birth Cohort 1966 (NFBC66). As part of the studies of this Finnish birth cohort genome-wide association analysis has recently been performed. Methodology In the present study, we re-analyzed the genome-wide association data with regard to these two measures of psychosis proneness, conditioning on our previous DISC1 observation. From the original NFBC66 sample (N = 12 058), 4 561 individuals provided phenotype and genotype data. No markers were significant at the genome-wide level. However, several genes with biological relevance to mental illnesses were highlighted through loci displaying suggestive evidence for association (≥3 SNP with P<10E-4). These included the protein coding genes, CXCL3, KIAA1128, LCT, MED13L, TMCO7, TTN, and the micro RNA MIR620. Conclusions By conditioning a previous genome-wide association study on DISC1, we have been able to identify eight genes as associating to psychosis proneness. Further, these molecules predominantly link to the DISC1 pathway, strengthening the evidence for the role of this gene network in the etiology of mental illness. The use of quantitative measures of psychosis proneness in a large population cohort will make these findings, once verified; more generalized to a broad selection of disorders related to psychoses and psychosis proneness.

These data suggest, but cannot establish, that breastfeeding in infancy may be associated with a small reduction in risk of ischemic cardiovascular disease in adulthood.

OBJECTIVES: Whether consumption of sugar-sweetened beverages (SSBs) or artificially sweetened beverages (ASBs) is associated with risk of breast cancer is of public health interest. Therefore, we aimed to evaluate associations between consumption of SSBs and ASBs with risk of total and subtype-specific breast cancer. METHODS: We followed 80,677 women from the Nurses’ Health Study (NHS; 1980 to 2016) and 86,115 women from the Nurses’ Health Study II (NHSII; 1991 to 2017) who were free from breast cancer at baseline. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: We documented 10,248 breast cancer cases during 3,990,008 person-years of follow-up. Consumption of SSBs or ASBs were not associated with total breast cancer risk; pooled HR (95% CI) comparing extreme categories were 1.05 (0.97, 1.15) and 0.97 (0.91, 1.03), respectively. In cohort-specific analysis, SSBs were associated with a higher risk of breast cancer in NHS (HR (≥1/day vs. < 1/month) 1.12; 95% CI 1.00, 1.24; P-trend = 0.03). We observed a significant interaction by BMI (P-interaction = 0.02), where a modestly higher risk of breast cancer with each serving per day increment of SSBs was found in lean women (BMI < 25 kg/m(2)) (HR, 1.06, 95% CI, 1.01, 1.12), but not among overweight or obese women (BMI ≥ 25 kg/m(2)) (HR, 0.98, 95% CI, 0.93, 1.04). Moreover, in the pooled, fully adjusted analysis, compared to infrequent consumers (<1/month), those who consumed ≥ 1 serving of ASBs per day had a lower risk of luminal A breast tumors (HR, 0.88; 95% CI, 0.78, 0.99; P-trend = 0.01). CONCLUSIONS: Although no significant associations were observed overall, consumption of SSBs was associated with a modest higher risk of breast cancer among lean women. This finding could have occurred by chance and needs confirmation. Our findings also suggest no substantial increase in risk of breast cancer with consumption of ASBs. FUNDING SOURCES: This study was supported by grants from the National Institutes of Health, and the Breast Cancer Research Foundation. ARN was supported by a fellowship from the Spanish Association Against Cancer Scientific Foundation (FC AECC). The funding sources did not participate in the design or conduct of the study; collection, management, analysis or interpretation of the data; or preparation, review, or approval of the manuscript.

ABSTRACT Identifying novel mechanisms underlying dementia is critical to improving prevention and treatment. As an approach to mechanistic discovery, we investigated whether MIND diet (Mediterranean-DASH Diet Intervention for Neurodegenerative Delay), a consistent risk factor for dementia, is correlated with a specific profile of cortical gene expression, and whether such a transcriptomic profile is associated with dementia, in the Religious Orders Study (ROS) and Rush Memory and Aging Project (MAP). RNA sequencing (RNA-Seq) was conducted in postmortem dorsolateral prefrontal cortex tissue from 1,204 deceased participants; neuropsychological assessments were performed annually prior to death. In a subset of 482 participants, diet was assessed ~6 years before death using a validated food-frequency questionnaire; in these participants, using elastic net regression, we identified a transcriptomic profile, consisting of 50 genes, significantly correlated with MIND diet score ( P =0.001). In multivariable analysis of the remaining 722 individuals, higher transcriptomic score of MIND diet was associated with slower annual rate of decline in global cognition (β=0.011 per standard deviation increment in transcriptomic profile score, P =0.003) and lower odds of dementia (odds ratio [OR] =0.76, P =0.0002). Cortical expression of several genes appeared to mediate the association between MIND diet and dementia, including TCIM , whose expression in inhibitory neurons and oligodendrocytes was associated with dementia in a subset of 424 individuals with single-nuclei RNA-seq data. In a secondary Mendelian randomization analysis, genetically predicted transcriptomic profile score was associated with dementia (OR=0.93, P =0.04). Our study suggests that associations between diet and cognitive health may involve brain molecular alterations at the transcriptomic level. Investigating brain molecular alterations related to diet may inform the identification of novel pathways underlying dementia.

In this study, higher MED intake was associated with approximately one-fourth relative risk reduction in CVD events, which could be explained in part by known risk factors, both traditional and novel.

Background: The association of weight gain from early to middle adulthood with a wide range of health outcomes later in life has not been systematically examined. Methods: We included 93,873 women from the Nurses’ Health Study and 25,374 men from the Health Professionals Follow-up Study who recalled weight at early adulthood (18 years in women, 21 years in men) and reported current weight in middle adulthood (55 years). Beginning from 55 years old, we prospectively followed them for incident cases of type 2 diabetes, hypertension, cardiovascular disease, cancer, three other medical conditions, and all-cause mortality. Among 51,185 women and 17,694 men who were at least 64 years of age in 2010, we also considered “healthy aging”, defined as no diagnosis of 11 major chronic diseases and no major cognitive impairment, physical impairment, or mental health limitations. Results: On average, female participants gained 12.55 kg (interquartile range: 14.36 kg) of body weight and males gained 9.68 kg (interquartile range: 11.19 kg) from early to middle adulthood. During a median follow-up of 18 years in women and 14 years in men, we documented 9360 incident cases of type 2 diabetes, 37,298 of hypertension, 9220 of cardiovascular disease, 20,222 of cancer (including 9458 of obesity-related cancers), 7438 of symptomatic cholelithiasis, 2702 of severe osteoarthritis, 31,960 of cataract extraction, and 27,250 deaths. In multivariate models, compared to those maintained stable weight (weight change &lt;2.5kg), participants who gained 20+ kg had increased risks of: diabetes (hazard ratio [HR, 95%CI], 10.93[9.65–12.39] in women, 8.19[6.41–10.46] in men), hypertension (2.24[2.15–2.34] in women, 2.11[1.91–2.33] in men), cardiovascular disease (1.87[1.72–2.04] in women, 1.72[1.40–2.11] in men), obesity-related cancers (1.53[1.41–1.66] in women, 1.27[0.95–1.69] in men), and mortality (1.43[1.37–1.50] in women, 1.34[1.18–1.51] in men); they had decreased odds of healthy aging (odds ratio [OR, 95%CI], 0.36[0.32–0.40] in women and 0.50[0.43–0.57] in men). In a meta-analysis combing both sexes, the increase in risk associated with each 10 kg weight gain was 71% for type 2 diabetes, 27% for hypertension, 17% for cardiovascular disease, 31% for symptomatic cholelithiasis, 15% for obesity-related cancers, 9% for severe osteoarthritis, 5% for cataract extraction, and 9% for mortality; for the same weight gain the odds of healthy aging was 28% lower. Conclusions: Our data provide strong evidence that weight gain from early to middle adulthood is associated with substantially increased risk of major chronic diseases and mortality, and overall decreased odds of aging with good health and well-being among women and men.

OBJECTIVE It is unclear whether changes in BMI during rapid economic development influence subsequent mortality. RESEARCH DESIGN AND METHODS We analyzed whether BMI in 1976 and 1994 and changes in BMI during 1976–1994 predict cardiovascular disease (CVD) and all-cause mortality in a 35-year follow-up cohort of 1,696 Chinese (1,124 men and 572 women, aged 35–65 years) in Xi'an, China. Participants were categorized as underweight (&amp;lt;18.5 kg/m2), normal weight (18.5–24.9 kg/m2), and overweight (≥25.0 kg/m2). RESULTS During 51,611 person-years of follow-up, we identified 655 deaths from all causes and 234 from CVD. From 1976 to 1994, the prevalence of overweight rose from 9.2 to 27.8%. With each unit increment in 1976 BMI, multivariate hazard ratios (HRs) (95% CI) were 0.78 (0.72–0.84) for CVD and 0.91 (0.87–0.95) for all-cause mortality. In contrast, corresponding HRs were 1.14 (1.08–1.19) and 1.05 (1.01–1.08) in 1994 BMI. The HRs for each unit increment in BMI change from 1976 to 1994 were 1.35 (1.25–1.41) for CVD and 1.09 (1.05–1.13) for all-cause mortality. Compared with participants with stable normal weight in 1976 and 1994, HRs of all-cause mortality for those who had normal weight in 1976 but became overweight in 1994 and for those who were persistently overweight during 1976–1994 were 1.42 (1.12–1.80) and 1.80 (1.04–3.14), respectively. CONCLUSIONS Gaining weight with increased BMI at middle age in Chinese during economic development was associated with elevated risks of all-cause and CVD mortality. Higher BMI measured before economic development was associated with lower mortality risk, whereas BMI measured afterward was associated with increased mortality.