Personality Factors and Subjective Cognitive Decline: The FACEHBI Cohort

Individuals with subjective cognitive decline (SCD) have the perception of memory problems without showing impairment on standardized cognitive tests. SCD has been associated with an increased risk of developing Alzheimer’s disease (AD). Neuroticism and openness personality dimensions have also been associated with SCD and AD. From the aforementioned, we aimed to ascertain whether the dimensions and traits defined by the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ) differentiate between individuals with SCD and the general population (GP). A total of 187 participants with SCD and mild affective symptomatology recruited from the Fundació ACE Health Brain Initiative (FACEHBI) project completed the ZKPQ. Each SCD participant was matched by sex and age to an individual from the GP. Both samples included 71 men and 116 women with a mean age of 65.9 years. Results indicated that the SCD group scored significantly lower in Neuroticism-Anxiety and Activity than the GP group. Only Activity remained statistically significant in a multivariate analysis. These findings suggest that individuals with SCD have a low energy level and a dislike for an active and busy life. From the obtained results and knowing additional physical activities may delay the conversion from normal aging to cognitive impairment, we encourage promoting this lifestyle in daily routine. The assessment of personality may result in an SCD plus feature, which may serve as an upgrading strategy for future research

Identification of a new locus and validation of previously reported loci showing differential methylation associated with smoking. The REGICOR study.

Smoking increases the risk of many diseases and could act through changes in DNA methylation patterns. The aims of this study were to determine the association between smoking and DNA methylation throughout the genome at cytosine-phosphate-guanine (CpG) site level and genomic regions. A discovery cross-sectional epigenome-wide association study nested in the follow-up of the REGICOR cohort was designed and included 645 individuals. Blood DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip. Smoking status was self-reported using a standardized questionnaire. We identified 66 differentially methylated CpG sites associated with smoking, located in 38 genes. In most of these CpG sites, we observed a trend among those quitting smoking to recover methylation levels typical of never smokers. A CpG site located in a novel smoking-associated gene (cg06394460 in LNX2) was hypomethylated in current smokers. Moreover, we validated two previously reported CpG sites (cg05886626 in THBS1, and cg24838345 in MTSS1) for their potential relation to atherosclerosis and cancer diseases, using several different approaches: CpG site methylation, gene expression, and plasma protein level determinations. Smoking was also associated with higher THBS1 gene expression but with lower levels of thrombospondin-1 in plasma. Finally, we identified differential methylation regions in 13 genes and in four non-coding RNAs. In summary, this study replicated previous findings and identified and validated a new CpG site located in LNX2 associated with smoking.This work was supported by the following sources: Agència de Gestió Ajuts 464 Universitaris de Recerca (2014 SGR 240); the Spanish Ministry of Economy through 465 the Carlos III Health Institute (ISCIII-FIS-FEDER-ERDF PI11-01801, PI08-1327, PI05-466 1251, PI05-1297, PI02-0471, FIS99/0013-01, FIS96/0026-01, FIS93/0568, 467 FIS92/0009-05), and the Red de Investigación Cardiovascular (RD12/0042/0061, 468 RD12/0042/0013). The BAsicMAR study was funded by the Spanish Ministry of 469 Economy through the Carlos III Health Institute (ISCIII-FIS-FEDER-ERDF) PI12/01238 470 and RecerCaixa JJ086116. Sergi Sayols-Baixeras was funded by a contract from 471 Instituto de Salud Carlos III FEDER (IFI14/00007)

Identification and validation of seven new loci showing differential DNA methylation related to serum lipid profile: an epigenome-wide approach. The REGICOR study.

Lipid traits (total, low-densityand high-density lipoproteincholesterol, and triglycerides) are risk factors for cardiovascular disease. DNA methylation is an inherited but also modifiable epigenetic mark that has been related tocardiovascular risk factors. Our aim was to identify loci showing differential DNA methylation related to serum lipid levels. Blood DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip. Atwo-stage epigenome-wide association study was performed, with a discovery sample intheREGICOR study (n=645)and validation in the Framingham Offspring Study (n=2,542).FourteenCpG sites located in 9 genes (SREBF1, SREBF2, PHOSPHO1, SYNGAP1, ABCG1, CPT1A, MYLIP, TXNIP andSLC7A11) and 2 intergenic regions showeddifferential methylation in association with lipid traits. Six of these genes and 1 intergenic region were new discoveries showing differential methylation relatedto total cholesterol (SREBF2), HDL-cholesterol (PHOSPHO1, SYNGAP1 and an intergenic region in chromosome 2) and triglycerides (MYLIP, TXNIP andSLC7A11).These CpGs explained0.7%, 9.5% and18.9% of the variability of total cholesterol, HDL cholesterol and triglycerides in the Framingham Offspring Study, respectively. The expression of the genesSREBF2and SREBF1was inversely associated with methylation of their corresponding CpGs(p-value=0.0042 and 0.0045, respectively) in participants of the GOLDN study(n=98). In turn, SREBF1expression wasdirectly associated with HDL cholesterol(p-value=0.0429). Genetic variants in SREBF1, PHOSPHO1, ABCG1and CPT1Awerealso associated with lipid profile. Further research is warranted to functionally validatethesenew loci and assess the causality ofnew and established associationsbetween these differentially methylated lociand lipid metabolism.This work was supported by the following sources: Agència de Gestio Ajuts Universitaris de Recerca [2014 SGR 240]; the Spanish Ministry of Economy through the Carlos III Health Institute [ISCIII-FIS-FEDER-ERDF PI12-00232, PI12-01238, PI11-01801, PI08-1327, PI05-1251, PI05-1297, PI02-0471, FIS99/0013-01, FIS96/0026-01, FIS93/0568, FIS92/0009-05], and the Red de Investigacion Cardiovascular [RD12/0042/0013, RD12/0042/0020, RD12/0042/0055, RD12/0042/0061]. S.S-B. was funded by a contract from Instituto de Salud Carlos III FEDER [IFI14/00007] and Daniel Bravo Andreu Private Foundation. GOLDN: The GOLDN study (AND, DA, JO, SA, DKA) was funded by the US National Institute of Health (NIH)/National Heart, Lung and Blood Institutes (http://www.nhlbi.nih.gov) grants R01HL104135 and U01HL72524

Identification of a new locus and validation of previously reported loci showing differential methylation associated with smoking. The REGICOR study.

Smoking increases the risk of many diseases and could act through changes in DNA methylation patterns. The aims of this study were to determine the association between smoking and DNA methylation throughout the genome at cytosine-phosphate-guanine (CpG) site level and genomic regions. A discovery cross-sectional epigenome-wide association study nested in the follow-up of the REGICOR cohort was designed and included 645 individuals. Blood DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip. Smoking status was self-reported using a standardized questionnaire. We identified 66 differentially methylated CpG sites associated with smoking, located in 38 genes. In most of these CpG sites, we observed a trend among those quitting smoking to recover methylation levels typical of never smokers. A CpG site located in a novel smoking-associated gene (cg06394460 in LNX2) was hypomethylated in current smokers. Moreover, we validated two previously reported CpG sites (cg05886626 in THBS1, and cg24838345 in MTSS1) for their potential relation to atherosclerosis and cancer diseases, using several different approaches: CpG site methylation, gene expression, and plasma protein level determinations. Smoking was also associated with higher THBS1 gene expression but with lower levels of thrombospondin-1 in plasma. Finally, we identified differential methylation regions in 13 genes and in four non-coding RNAs. In summary, this study replicated previous findings and identified and validated a new CpG site located in LNX2 associated with smoking.This work was supported by the following sources: Agència de Gestió Ajuts 464 Universitaris de Recerca (2014 SGR 240); the Spanish Ministry of Economy through 465 the Carlos III Health Institute (ISCIII-FIS-FEDER-ERDF PI11-01801, PI08-1327, PI05-466 1251, PI05-1297, PI02-0471, FIS99/0013-01, FIS96/0026-01, FIS93/0568, 467 FIS92/0009-05), and the Red de Investigación Cardiovascular (RD12/0042/0061, 468 RD12/0042/0013). The BAsicMAR study was funded by the Spanish Ministry of 469 Economy through the Carlos III Health Institute (ISCIII-FIS-FEDER-ERDF) PI12/01238 470 and RecerCaixa JJ086116. Sergi Sayols-Baixeras was funded by a contract from 471 Instituto de Salud Carlos III FEDER (IFI14/00007)

Author Correction: Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing (Nature Genetics, (2019), 51, 3, (414-430), 10.1038/s41588-019-0358-2)

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Author Correction: Genetic meta-analysis of diagnosed Alzheimer\u27s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.

An amendment to this paper has been published and can be accessed via a link at the top of the paper