Abstract：
:To identify loci associated with Alzheimer disease, we conducted a three-stage analysis using existing genome-wide association studies (GWAS) and genotyping in a new sample. In Stage I, all suggestive single-nucleotide polymorphisms (at P<0.001) in a previously reported GWAS of seven independent studies (8082 Alzheimer's disease (AD) cases; 12 040 controls) were selected, and in Stage II these were examined in an in silico analysis within the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium GWAS (1367 cases and 12904 controls). Six novel signals reaching P<5 × 10(-6) were genotyped in an independent Stage III sample (the Fundació ACE data set) of 2200 sporadic AD patients and 2301 controls. We identified a novel association with AD in the adenosine triphosphate (ATP) synthase, H+ transporting, mitochondrial F0 (ATP5H)/Potassium channel tetramerization domain-containing protein 2 (KCTD2) locus, which reached genome-wide significance in the combined discovery and genotyping sample (rs11870474, odds ratio (OR)=1.58, P=2.6 × 10(-7) in discovery and OR=1.43, P=0.004 in Fundació ACE data set; combined OR=1.53, P=4.7 × 10(-9)). This ATP5H/KCTD2 locus has an important function in mitochondrial energy production and neuronal hyperpolarization during cellular stress conditions, such as hypoxia or glucose deprivation.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Boada M,Antúnez C,Ramírez-Lorca R,DeStefano AL,González-Pérez A,Gayán J,López-Arrieta J,Ikram MA,Hernández I,Marín J,Galán JJ,Bis JC,Mauleón A,Rosende-Roca M,Moreno-Rey C,Gudnasson V,Morón FJ,Velasco J,Carrasco JM,Adoi
10.1038/mp.2013.86subject
Has Abstractpub_date
2014-06-01 00:00:00pages
682-7issue
6eissn
1359-4184issn
1476-5578pii
mp201386journal_volume
19pub_type
杂志文章,meta分析abstract：:The actions of CRF in the brain and in the periphery are mediated through multiple binding sites. There are three receptors, CRF1, CRF2 alpha and CRF2 beta, which encode 411, 415 and 431 amino acid proteins and transduce signals via the stimulation of intracellular cAMP production. The recent identification of high-af...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：
更新日期：1996-09-01 00:00:00
abstract：:Impulsivity, a multifaceted behavioral hallmark of attention-deficit/hyperactivity disorder (ADHD), strongly influences addiction vulnerability and other psychiatric disorders that incur enormous medical and societal burdens yet the neurobiological underpinnings linking impulsivity to disease remain poorly understood....
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2017.80
更新日期：2018-05-01 00:00:00
abstract：:Multiple lines of evidence point to glutamatergic signaling in the postsynaptic density (PSD) as a pathophysiologic mechanism in schizophrenia. Integral to PSD glutamatergic signaling is reciprocal interplay between GluN and mGluR5 signaling. We examined agonist-induced mGluR5 signaling in the postmortem dorsolateral ...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-018-0234-y
更新日期：2020-04-01 00:00:00
abstract：:Several lines of evidence implicate dopa decarboxylase (DDC) with schizophrenia. By analysis of two putative functional DDC variants in 173 schizophrenic patients and 204 controls we tested the hypotheses that DDC is involved in: (1) predisposition to schizophrenia; and (2) modulation of age at disease onset. No assoc...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4000902
更新日期：2001-11-01 00:00:00
abstract：:Genetic factors do not fully account for the relatively high heritability of neurodevelopmental conditions, suggesting that non-genetic heritable factors contribute to their etiology. To evaluate the potential contribution of aberrant thyroid hormone status to the epigenetic inheritance of neurological phenotypes, we ...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-018-0281-4
更新日期：2020-05-01 00:00:00
abstract：:There are well-replicated, independent lines of evidence supporting a role for corticotropin-releasing hormone (CRH) in the pathophysiology of depression. CRH receptor 1 (CRHR1), which we first mapped in the brain in 1994, has been implicated in the treatment of depression and anxiety. We studied the association of CR...
journal_title：Molecular psychiatry
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1038/sj.mp.4001587
更新日期：2004-12-01 00:00:00
abstract：:The hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of a variety of mood and cognitive disorders. Neuroendocrine studies have demonstrated HPA axis overactivity in major depression, a relationship of HPA axis activity to cognitive performance and a potential role of HPA axis geneti...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2016.120
更新日期：2017-04-01 00:00:00
abstract：:Converging advances in the fields of molecular biology, molecular genetics, cellular biology and embryology have given researchers the tools for the targeted delivery and stable germline transmission of foreign genes (transgenes) in the mouse. In the realm of neuropsychiatry, this so-named transgenic technology has be...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：
更新日期：1996-05-01 00:00:00
abstract：:A genetic predisposition to the development of neuroleptic malignant syndrome (NMS) has been suggested by clinical studies. Although the molecular basis of NMS is unclear, a dopaminergic blockade mechanism has been considered the main cause. We therefore investigated the association between NMS and three functional po...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4001422
更新日期：2004-03-01 00:00:00
abstract：:Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals born in Denmark since 1...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2013.2
更新日期：2014-03-01 00:00:00
abstract：:Leptin is a hormone with pleiotropic functions affecting several tissues. Because leptin has a crucial role in the adaptation of an organism to semi-starvation, anorexia nervosa (AN) serves as a model disorder to elucidate the functional implications of hypoleptinaemia; vice versa, several symptoms in patients with th...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/sj.mp.4001909
更新日期：2007-01-01 00:00:00
abstract：:This corrects the article DOI: 10.1038/mp.2017.5. ...
journal_title：Molecular psychiatry
pub_type： 杂志文章,已发布勘误
doi：10.1038/mp.2017.70
更新日期：2018-03-01 00:00:00
abstract：:Medical treatment with various cytokines can provoke psychiatric symptoms. Conversely, psychiatric patients can display abnormalities in cytokine and neurotrophic factor expression. Such observations have pointed to the potential contribution of cytokines and growth factors to schizophrenic pathology and/or etiology. ...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/sj.mp.4000730
更新日期：2000-11-01 00:00:00
abstract：:Serum antibodies against amyloid-β peptide (Aβ) in humans with or without diagnosis of Alzheimer's disease (AD) indicate the possibility of immune responses against brain antigens. In an unbiased screening for antibodies directed against brain proteins, we found in AD patients high serum levels of antibodies against t...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2012.70
更新日期：2013-03-01 00:00:00
abstract：:Induction of neuroprotective heat-shock proteins via pharmacological Hsp90 inhibitors is currently being investigated as a potential treatment for neurodegenerative diseases. Two major hurdles for therapeutic use of Hsp90 inhibitors are systemic toxicity and limited central nervous system permeability. We demonstrate ...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2016.104
更新日期：2017-07-01 00:00:00
abstract：:In our genome scan for schizophrenia genes in 265 Irish pedigrees, marker D5S818 in 5q22 produced the second best result of the first 223 markers tested (P = 0.002). We then tested an additional 13 markers and the evidence suggests the presence of a vulnerability locus for schizophrenia in region 5q22-31. This region ...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4000258
更新日期：1997-03-01 00:00:00
abstract：:Attention deficit hyperactivity disorder, combined type (ADHD-CT) is associated with spatial working memory deficits. These deficits are known to be subserved by dysfunction of neural circuits involving right prefrontal, striatal and parietal brain regions. This study determines whether decreased right prefrontal, str...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4001999
更新日期：2007-09-01 00:00:00
abstract：:In developing his mature concept of hebephrenic dementia praecox (DP) in his 4th (1893) through 6th textbook editions (1899), Kraepelin worked from the hebephrenic syndrome first described by Hecker (1871) and then carefully studied by his student Daraszkiewicz (1892). Working under Kraepelin's supervision, Daraszkiew...
journal_title：Molecular psychiatry
pub_type： 历史文章,杂志文章,评审
doi：10.1038/s41380-019-0411-7
更新日期：2020-01-01 00:00:00
abstract：:We conducted a 10 centimorgan (cM) linkage genome scan in a set of American extended pedigrees ascertained through probands with panic disorder. Several anxiety disorders segregate in these families. In this article, we describe results for simple phobia from 14 of these families (including 129 subjects of whom 57 are...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4001224
更新日期：2003-01-01 00:00:00
abstract：:Schizophrenia is a severe neurodevelopmental psychiatric affliction manifested behaviorally at late adolescence/early adulthood. Current treatments comprise antipsychotics which act solely symptomatic, are limited in their effectiveness and often associated with side-effects. We here report that application of non-inv...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-019-0356-x
更新日期：2020-04-01 00:00:00
abstract：:Chromosome 1q has been implicated in the etiology of schizophrenia in several independent studies. However, the peak linkage findings have been dispersed over a large chromosomal region, with negative findings in this region also being reported. Our group has previously observed linkage on chromosome 1q42, maximizing ...
journal_title：Molecular psychiatry
pub_type： 临床试验,杂志文章
doi：10.1038/sj.mp.4001536
更新日期：2004-11-01 00:00:00
abstract：:Genomic risk profile scores (GRPSs) have been shown to predict case-control status of schizophrenia (SCZ), albeit with varying sensitivity and specificity. The extent to which this variability in prediction accuracy is related to differences in sampling strategies is unknown. Danish population-based registers and Neon...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2015.130
更新日期：2016-07-01 00:00:00
abstract：:The human serotonin transporter gene (5-HTT) demonstrates two polymorphisms with possible functional impact: a 44-bp insertion/deletion polymorphism of the promoter region and a 17-bp variable number of tandem repeat polymorphism (VNTR) in intron 2 (STin2). Such genetic polymorphisms in the serotoninergic system may i...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4000821
更新日期：2001-03-01 00:00:00
abstract：:Adults with psychotic disorders have dysconnectivity in critical brain networks, including the default mode (DM) and the cingulo-opercular (CO) networks. However, it is unknown whether such deficits are present in youth with less severe symptoms. We conducted a multivariate connectome-wide association study examining ...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2015.66
更新日期：2015-12-01 00:00:00
abstract：:Studying genetic determinants of intermediate phenotypes is a powerful tool to increase our understanding of genotype-phenotype correlations. Metabolic traits pertinent to the central nervous system (CNS) constitute a potentially informative target for genetic studies of intermediate phenotypes as their genetic underp...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2012.183
更新日期：2014-02-01 00:00:00
abstract：:APAF1, encoding the protein apoptosis protease activating factor 1 (Apaf-1), has recently been established as a chromosome 12 gene conferring predisposition to major depression in humans. The molecular phenotypes of Apaf-1 variants were determined by in vitro reconstruction of the apoptosome complex in which Apaf-1 ac...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4001755
更新日期：2006-01-01 00:00:00
abstract：:In the Table 1 legend, the reference numbers and symbols were not correctly presented in the footnotes. The corrected footnotes are presented below. ...
journal_title：Molecular psychiatry
pub_type： 杂志文章,已发布勘误
doi：10.1038/s41380-018-0026-4
更新日期：2019-03-01 00:00:00
abstract：:Suicide is a major public health concern and a leading cause of death in most societies. Suicidal behaviour is complex and heterogeneous, likely resulting from several causes. It associates with multiple factors, including psychopathology, personality traits, early-life adversity and stressful life events, among other...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/mp.2017.141
更新日期：2017-10-01 00:00:00
abstract：:Cigarette smoking is more prevalent in subjects with schizophrenia compared to those with other psychiatric disorders or the general population and could therefore affect molecular pathways that impact the pathophysiology of this disorder. As smoking is also known to suppress immune responses, we investigated the effe...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2008.120
更新日期：2010-04-01 00:00:00
abstract：:The 'neurodegeneration with brain iron accumulation' (NBIA) disease family entails movement or cognitive impairment, often with psychiatric features. To understand how iron loading affects the brain, we studied mice with disruption of two iron regulatory genes, hemochromatosis (Hfe) and transferrin receptor 2 (Tfr2). ...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2015.192
更新日期：2016-11-01 00:00:00
