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271.
  • Zetterberg, Henrik, 1973, et al. (författare)
  • Biomarkers for Alzheimer's disease-preparing for a new era of disease-modifying therapies.
  • 2021
  • Ingår i: Molecular psychiatry. - 1476-5578. ; 26:1, s. 296-308
  • Forskningsöversikt (refereegranskat)abstract
    • Clinical trial results presented in 2019 suggest that antibody-based removal of cerebral amyloid β (Aβ) plaques may possibly clear tau tangles and modestly slow cognitive decline in symptomatic Alzheimer's disease (AD). Although regulatory approval of this approach is still pending, preparing the healthcare system for the advent of disease-modifying therapies against AD is imperative. In particular, it will be necessary to identify the most suitable biomarkers to facilitate appropriate treatment of AD. Here, we give an update on recent developments in fluid and imaging biomarkers for AD-related pathologies and discuss potential approaches that could be adopted to screen for and clarify the underlying pathology in people seeking medical advice because of cognitive symptoms. We succinctly review recent data regarding biomarkers for Aβ and tau pathology, neurodegeneration, synaptic dysfunction, and inflammation, highlight the need for further research into common copathologies, and suggest how different biomarkers could be used (most likely in combination) to facilitate the development and clinical implementation of novel drug candidates against AD.
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272.
  • Zhang, Ruyue, et al. (författare)
  • Familial co-aggregation of schizophrenia and eating disorders in Sweden and Denmark
  • 2021
  • Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 26:9, s. 5389-5397
  • Tidskriftsartikel (refereegranskat)abstract
    • Eating disorders and schizophrenia are both moderately to highly heritable and share significant genetic risk despite distinct diagnostic criteria. Large-scale family studies on the co-aggregation of these disorders are lacking. Thus, we aimed to estimate the co-occurrence and familial co-aggregation of these disorders within the entire Swedish and Danish population. The proband cohort consisted of individuals born in Sweden (1977-2003) and Denmark (1984-2006) and still residing in their respective country at age six (NSweden = 2,535,191, NDenmark = 1,382,367). Probands were linked to their biological parents, siblings, grandparents, uncles/aunts, and cousins. Diagnoses for anorexia nervosa (AN) and other eating disorders (OED: bulimia nervosa, binge-eating disorder, and eating disorder not otherwise specified) for probands and schizophrenia diagnoses for both probands and relatives were obtained. The likelihood of having schizophrenia in those with AN or OED and their relatives was compared with individuals without eating disorder diagnoses and their relatives. Probands with AN or OED were more likely to have schizophrenia than probands without these disorders. All relatives of probands with AN or OED (except parents and uncles/aunts of probands with AN) were at increased risk of schizophrenia. In general, the magnitude of odds ratios attenuated with decreasing genetic relatedness. These results suggest familial liability contributes to the association between eating disorders and schizophrenia. Clinicians should be mindful of this comorbid and co-aggregation pattern as it may influence case conceptualization and treatment decisions.
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273.
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274.
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275.
  • Zwir, Igor, et al. (författare)
  • Three Genetic-Environmental Networks for Human Personality
  • 2021
  • Ingår i: Molecular Psychiatry. - 1359-4184 .- 1476-5578. ; 26
  • Tidskriftsartikel (refereegranskat)abstract
    • Phylogenetic, developmental, and brain-imaging studies suggest that human personality is the integrated expression of three major systems of learning and memory that regulate (1) associative conditioning, (2) intentionality, and (3) self-awareness. We have uncovered largely disjoint sets of genes regulating these dissociable learning processes in different clusters of people with (1) unregulated temperament profiles (i.e., associatively conditioned habits and emotional reactivity), (2) organized character profiles (i.e., intentional self-control of emotional conflicts and goals), and (3) creative character profiles (i.e., self-aware appraisal of values and theories), respectively. However, little is known about how these temperament and character components of personality are jointly organized and develop in an integrated manner. In three large independent genome-wide association studies from Finland, Germany, and Korea, we used a data-driven machine learning method to uncover joint phenotypic networks of temperament and character and also the genetic networks with which they are associated. We found three clusters of similar numbers of people with distinct combinations of temperament and character profiles. Their associated genetic and environmental networks were largely disjoint, and differentially related to distinct forms of learning and memory. Of the 972 genes that mapped to the three phenotypic networks, 72% were unique to a single network. The findings in the Finnish discovery sample were blindly and independently replicated in samples of Germans and Koreans. We conclude that temperament and character are integrated within three disjoint networks that regulate healthy longevity and dissociable systems of learning and memory by nearly disjoint sets of genetic and environmental influences.
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276.
  • Zwir, Igor, et al. (författare)
  • Uncovering the complex genetics of human character
  • 2020
  • Ingår i: Molecular Psychiatry. - 1359-4184 .- 1476-5578. ; 25:10, s. 2295-2312
  • Tidskriftsartikel (refereegranskat)abstract
    • Human personality is 30–60% heritable according to twin and adoption studies. Hundreds of genetic variants are expected to influence its complex development, but few have been identified. We used a machine learning method for genome-wide association studies (GWAS) to uncover complex genotypic–phenotypic networks and environmental interactions. The Temperament and Character Inventory (TCI) measured the self-regulatory components of personality critical for health (i.e., the character traits of self-directedness, cooperativeness, and self-transcendence). In a discovery sample of 2149 healthy Finns, we identified sets of single-nucleotide polymorphisms (SNPs) that cluster within particular individuals (i.e., SNP sets) regardless of phenotype. Second, we identified five clusters of people with distinct profiles of character traits regardless of genotype. Third, we found 42 SNP sets that identified 727 gene loci and were significantly associated with one or more of the character profiles. Each character profile was related to different SNP sets with distinct molecular processes and neuronal functions. Environmental influences measured in childhood and adulthood had small but significant effects. We confirmed the replicability of 95% of the 42 SNP sets in healthy Korean and German samples, as well as their associations with character. The identified SNPs explained nearly all the heritability expected for character in each sample (50 to 58%). We conclude that self-regulatory personality traits are strongly influenced by organized interactions among more than 700 genes despite variable cultures and environments. These gene sets modulate specific molecular processes in brain for intentional goal-setting, self-reflection, empathy, and episodic learning and memory.
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277.
  • Zwir, Igor, et al. (författare)
  • Uncovering the complex genetics of human temperament
  • 2020
  • Ingår i: Molecular Psychiatry. - 1359-4184 .- 1476-5578. ; 25:10, s. 2275-2294
  • Tidskriftsartikel (refereegranskat)abstract
    • Experimental studies of learning suggest that human temperament may depend on the molecular mechanisms for associative conditioning, which are highly conserved in animals. The main genetic pathways for associative conditioning are known in experimental animals, but have not been identified in prior genome-wide association studies (GWAS) of human temperament. We used a data-driven machine learning method for GWAS to uncover the complex genotypic–phenotypic networks and environmental interactions related to human temperament. In a discovery sample of 2149 healthy Finns, we identified sets of single-nucleotide polymorphisms (SNPs) that cluster within particular individuals (i.e., SNP sets) regardless of phenotype. Second, we identified 3 clusters of people with distinct temperament profiles measured by the Temperament and Character Inventory regardless of genotype. Third, we found 51 SNP sets that identified 736 gene loci and were significantly associated with temperament. The identified genes were enriched in pathways activated by associative conditioning in animals, including the ERK, PI3K, and PKC pathways. 74% of the identified genes were unique to a specific temperament profile. Environmental influences measured in childhood and adulthood had small but significant effects. We confirmed the replicability of the 51 Finnish SNP sets in healthy Korean (90%) and German samples (89%), as well as their associations with temperament. The identified SNPs explained nearly all the heritability expected in each sample (37–53%) despite variable cultures and environments. We conclude that human temperament is strongly influenced by more than 700 genes that modulate associative conditioning by molecular processes for synaptic plasticity and long-term memory.
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278.
  • Sonestedt, Emily, et al. (författare)
  • Variation in fasting and non-fasting serum enterolactone concentrations in women of the Malmo Diet and Cancer cohort
  • 2008
  • Ingår i: European Journal of Clinical Nutrition. - : Nature Publishing Group. - 1476-5640. ; 62:8, s. 1005-1009
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives:The aim of this study was to examine the variation of enterolactone from fasting and non-fasting blood of middle-aged healthy women eating a normal diet to determine the usefulness of a single sample in epidemiological studies.Subjects and methods:Twenty-six women born between 1940 and 1950 were recruited within the Malmo Diet and Cancer cohort. Three non-fasting and two overnight fasting samples were collected from each individual during a 5-week period. Twenty-one participated in all measurements. Enterolactone concentrations were analyzed by time-resolved fluoroimmunoassay.Results:The within-subject and between-subject variations (coefficient of variations, CV) were estimated to 59 and 89% respectively for fasting samples and 71 and 67% for non-fasting samples. The intraclass correlation coefficients (ICC) were estimated to 0.66 (95% confidence interval (CI) 0.35-0.84) for fasting and 0.48 (95% CI, 0.22-0.72) for non-fasting samples.Conclusions:Although the estimated ICC for blood samples was moderate, it indicates that enterolactone levels of both fasting and non-fasting blood samples should be useful in future projects within the Malmo Diet and Cancer cohort.European Journal of Clinical Nutrition advance online publication, 30 May 2007; doi:10.1038/sj.ejcn.1602811.
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