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Article ; Online: Leveraging Health Linkage Data From the UK Biobank-With Great Power Comes Great Responsibility-Reply.

Amin, Najaf / Kaddurah-Daouk, Rima / van Duijn, Cornelia M

2023 Volume 80, Issue 10, Page(s) 1077–1078

Language	English
Publishing date	2023-08-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2701203-7
ISSN	2168-6238 ; 2168-622X
ISSN (online)	2168-6238
ISSN	2168-622X
DOI	10.1001/jamapsychiatry.2023.2969
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Article ; Online: The Role of Gut Microbiota in Neuropsychiatric Diseases - Creation of An Atlas-Based on Quantified Evidence.

Bonnechère, Bruno / Amin, Najaf / van Duijn, Cornelia

Frontiers in cellular and infection microbiology

2022 Volume 12, Page(s) 831666

Abstract: There is a growing body of evidence highlighting the significant role of gut microbiota in various pathologies. We performed a systematic review to review the different microbiota involved in neuropsychiatric diseases. 50 studies (23 studies for autism ... ...

Abstract	There is a growing body of evidence highlighting the significant role of gut microbiota in various pathologies. We performed a systematic review to review the different microbiota involved in neuropsychiatric diseases. 50 studies (23 studies for autism spectrum disorders, 18 for major depression, and 9 for schizophrenia), representing 2,137 patients and 2,844 controls. Concerning the microbiota, the genera
MeSH term(s)	Autism Spectrum Disorder ; Brain/microbiology ; Gastrointestinal Microbiome ; Humans ; Microbiota ; Probiotics
Language	English
Publishing date	2022-03-14
Publishing country	Switzerland
Document type	Journal Article ; Review ; Systematic Review
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2022.831666
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Article ; Online: What Are the Key Gut Microbiota Involved in Neurological Diseases? A Systematic Review.

Bonnechère, Bruno / Amin, Najaf / van Duijn, Cornelia

International journal of molecular sciences

2022 Volume 23, Issue 22

Abstract: There is a growing body of evidence highlighting there are significant changes in the gut microbiota composition and relative abundance in various neurological disorders. We performed a systematic review of the different microbiota altered in a wide ... ...

Abstract	There is a growing body of evidence highlighting there are significant changes in the gut microbiota composition and relative abundance in various neurological disorders. We performed a systematic review of the different microbiota altered in a wide range of neurological disorders (Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis, and stroke). Fifty-two studies were included representing 5496 patients. At the genus level, the most frequently involved microbiota are Akkermansia, Faecalibacterium, and Prevotella. The overlap between the pathologies was strongest for MS and PD, sharing eight genera (Akkermansia, Butyricicoccus, Bifidobacterium, Coprococcus, Dorea, Faecalibacterium, Parabacteroides, and Prevotella) and PD and stroke, sharing six genera (Enterococcus, Faecalibacterium, Lactobacillus, Parabacteroides, Prevotella, and Roseburia). The identification signatures overlapping for AD, PD, and MS raise the question of whether these reflect a common etiology or rather common consequence of these diseases. The interpretation is hampered by the low number and low power for AD, ALS, and stroke with ample opportunity for false positive and false negative findings.
MeSH term(s)	Humans ; Gastrointestinal Microbiome ; Nervous System Diseases ; Parkinson Disease/microbiology ; Microbiota ; Akkermansia ; Multiple Sclerosis/microbiology ; Prevotella ; Clostridiaceae ; Clostridiales ; Stroke
Language	English
Publishing date	2022-11-08
Publishing country	Switzerland
Document type	Systematic Review ; Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232213665
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Article ; Online: Does ethnicity influence dementia, stroke and mortality risk? Evidence from the UK Biobank.

Bonnechère, Bruno / Liu, Jun / Thompson, Alexander / Amin, Najaf / van Duijn, Cornelia

Frontiers in public health

2023 Volume 11, Page(s) 1111321

Abstract: Introduction: The number of people with dementia and stroke is increasing worldwide. There is increasing evidence that there are clinically relevant genetic differences across ethnicities. This study aims to quantify risk factors of dementia, stroke, ... ...

Abstract	Introduction: The number of people with dementia and stroke is increasing worldwide. There is increasing evidence that there are clinically relevant genetic differences across ethnicities. This study aims to quantify risk factors of dementia, stroke, and mortality in Asian and black participants compared to whites. Methods: 272,660 participants from the UK Biobank were included in the final analysis, among whom the vast majority are white ( Results: After adjusting for risk factors, black participants have an increased risk of dementia and stroke compared to white participants, while Asians has similar odds to the white. The risk of mortality is not different in blacks and white participants but Asians have a decreased risk. Discussion: The study provides important insights into the potential differences in the risk of dementia and stroke among different ethnic groups. Specifically, the study found that black individuals had a higher incidence of dementia and stroke compared to white individuals living in the UK. These findings are particularly significant as they suggest that there may be underlying factors that contribute to these differences, including genetic, environmental, and social factors. By identifying these differences, the study helps to inform interventions and policies aimed at reducing the risk of dementia and stroke, particularly among high-risk populations.
MeSH term(s)	Humans ; Biological Specimen Banks ; Dementia/epidemiology ; Ethnicity ; Stroke/epidemiology ; United Kingdom/epidemiology ; White People ; Asian People ; Black People
Language	English
Publishing date	2023-04-14
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2711781-9
ISSN	2296-2565 ; 2296-2565
ISSN (online)	2296-2565
ISSN	2296-2565
DOI	10.3389/fpubh.2023.1111321
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Article ; Online: Glaucoma Patients Have a Lower Abundance of Butyrate-Producing Taxa in the Gut.

Vergroesen, Joëlle E / Jarrar, Zakariya A / Weiss, Stefan / Frost, Fabian / Ansari, Abdus S / Nguyen, Picard / Kraaij, Robert / Medina-Gomez, Carolina / Völzke, Henry / Tost, Frank / Amin, Najaf / van Duijn, Cornelia M / Klaver, Caroline C W / Jürgens, Clemens / Hammond, Chris J / Ramdas, Wishal D

Investigative ophthalmology & visual science

2024 Volume 65, Issue 2, Page(s) 7

Abstract: Purpose: Glaucoma is an eye disease that is the most common cause of irreversible blindness worldwide. It has been suggested that gut microbiota can produce reactive oxygen species and pro-inflammatory cytokines that may travel from the gastric mucosa ... ...

Abstract	Purpose: Glaucoma is an eye disease that is the most common cause of irreversible blindness worldwide. It has been suggested that gut microbiota can produce reactive oxygen species and pro-inflammatory cytokines that may travel from the gastric mucosa to distal sites, for example, the optic nerve head or trabecular meshwork. There is evidence for a gut-eye axis, as microbial dysbiosis has been associated with retinal diseases. We investigated the microbial composition in patients with glaucoma and healthy controls. Moreover, we analyzed the association of the gut microbiome with intraocular pressure (IOP; risk factor of glaucoma) and vertical cup-to-disc ratio (VCDR; quantifying glaucoma severity). Methods: The discovery analyses included participants of the Rotterdam Study and the Erasmus Glaucoma Cohort. A total of 225 patients with glaucoma and 1247 age- and sex-matched participants without glaucoma were included in our analyses. Stool samples were used to generate 16S rRNA gene profiles. We assessed associations with 233 genera and species. We used data from the TwinsUK and the Study of Health in Pomerania (SHIP) to replicate our findings. Results: Several butyrate-producing taxa (e.g. Butyrivibrio, Caproiciproducens, Clostridium sensu stricto 1, Coprococcus 1, Ruminococcaceae UCG 007, and Shuttleworthia) were less abundant in people with glaucoma compared to healthy controls. The same taxa were also associated with lower IOP and smaller VCDR. The replication analyses confirmed the findings from the discovery analyses. Conclusions: Large human studies exploring the link between the gut microbiome and glaucoma are lacking. Our results suggest that microbial dysbiosis plays a role in the pathophysiology of glaucoma.
MeSH term(s)	Humans ; Butyrates ; Dysbiosis ; RNA, Ribosomal, 16S/genetics ; Glaucoma ; Optic Disk
Chemical Substances	Butyrates ; RNA, Ribosomal, 16S
Language	English
Publishing date	2024-02-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.65.2.7
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Article ; Online: Gut microbiome-wide association study of depressive symptoms.

Radjabzadeh, Djawad / Bosch, Jos A / Uitterlinden, André G / Zwinderman, Aeilko H / Ikram, M Arfan / van Meurs, Joyce B J / Luik, Annemarie I / Nieuwdorp, Max / Lok, Anja / van Duijn, Cornelia M / Kraaij, Robert / Amin, Najaf

Nature communications

2022 Volume 13, Issue 1, Page(s) 7128

Abstract: Depression is one of the most poorly understood diseases due to its elusive pathogenesis. There is an urgency to identify molecular and biological mechanisms underlying depression and the gut microbiome is a novel area of interest. Here we investigate ... ...

Abstract	Depression is one of the most poorly understood diseases due to its elusive pathogenesis. There is an urgency to identify molecular and biological mechanisms underlying depression and the gut microbiome is a novel area of interest. Here we investigate the relation of fecal microbiome diversity and composition with depressive symptoms in 1,054 participants from the Rotterdam Study cohort and validate these findings in the Amsterdam HELIUS cohort in 1,539 subjects. We identify association of thirteen microbial taxa, including genera Eggerthella, Subdoligranulum, Coprococcus, Sellimonas, Lachnoclostridium, Hungatella, Ruminococcaceae (UCG002, UCG003 and UCG005), LachnospiraceaeUCG001, Eubacterium ventriosum and Ruminococcusgauvreauiigroup, and family Ruminococcaceae with depressive symptoms. These bacteria are known to be involved in the synthesis of glutamate, butyrate, serotonin and gamma amino butyric acid (GABA), which are key neurotransmitters for depression. Our study suggests that the gut microbiome composition may play a key role in depression.
Language	English
Publishing date	2022-12-06
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-34502-3
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Article ; Online: The long-term relation between physical activity and executive function in the Rotterdam Study.

Galle, Sara A / Liu, Jun / Bonnechère, Bruno / Amin, Najaf / Milders, Maarten M / Deijen, Jan Berend / Scherder, Erik J A / Drent, Madeleine L / Voortman, Trudy / Ikram, M Arfan / van Duijn, Cornelia M

European journal of epidemiology

2022 Volume 38, Issue 1, Page(s) 71–81

Abstract: Background: Research on the association between physical inactivity and cognitive decline and dementia is dominated by studies with short-term follow-up, that might be biased by reverse causality.: Objective: Investigate the long-term association ... ...

Abstract	Background: Research on the association between physical inactivity and cognitive decline and dementia is dominated by studies with short-term follow-up, that might be biased by reverse causality. Objective: Investigate the long-term association between physical activity, cognition, and the rate of age-associated cognitive decline. Methods: We investigated the association between late-life physical activity and executive functioning and rate of decline of executive abilities during follow-up of up to 16 years, in 3553 participants of the prospective Rotterdam Study cohort. Measurement took place in 1997-1999, 2002-2004, 2009-2011, and 2014-2015. Results: At baseline (age ± 72 years), higher levels of physical activity were associated with higher levels of executive functioning (adjusted mean difference = 0.03, 95% CI: 0.00 0.06, p = 0.03). This difference remained intact up to 16 years of follow-up. The level of physical activity at baseline was unrelated to the rate of decline of executive abilities over time, in the whole group (adjusted mean difference in change Conclusion: Higher levels of physical activity in late adulthood are related to higher levels of executive functioning, up to 16 years of follow-up. Accelerated decline of executive abilities observed in those with the ApoE-ε4 allele might be mitigated by higher levels of physical activity.
MeSH term(s)	Humans ; Alleles ; Apolipoprotein E4/genetics ; Apolipoproteins E/genetics ; Cognitive Dysfunction ; Executive Function ; Genotype ; Neuropsychological Tests ; Prospective Studies ; Exercise ; Aged ; Aged, 80 and over
Chemical Substances	Apolipoprotein E4 ; Apolipoproteins E
Language	English
Publishing date	2022-09-27
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	632614-6
ISSN	1573-7284 ; 0393-2990
ISSN (online)	1573-7284
ISSN	0393-2990
DOI	10.1007/s10654-022-00902-4
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Article ; Online: Interplay of Metabolome and Gut Microbiome in Individuals With Major Depressive Disorder vs Control Individuals.

JAMA psychiatry

2023 Volume 80, Issue 6, Page(s) 597–609

Abstract: Importance: Metabolomics reflect the net effect of genetic and environmental influences and thus provide a comprehensive approach to evaluating the pathogenesis of complex diseases, such as depression.: Objective: To identify the metabolic signatures ...

Abstract	Importance: Metabolomics reflect the net effect of genetic and environmental influences and thus provide a comprehensive approach to evaluating the pathogenesis of complex diseases, such as depression. Objective: To identify the metabolic signatures of major depressive disorder (MDD), elucidate the direction of associations using mendelian randomization, and evaluate the interplay of the human gut microbiome and metabolome in the development of MDD. Design, setting and participants: This cohort study used data from participants in the UK Biobank cohort (n = 500 000; aged 37 to 73 years; recruited from 2006 to 2010) whose blood was profiled for metabolomics. Replication was sought in the PREDICT and BBMRI-NL studies. Publicly available summary statistics from a 2019 genome-wide association study of depression were used for the mendelian randomization (individuals with MDD = 59 851; control individuals = 113 154). Summary statistics for the metabolites were obtained from OpenGWAS in MRbase (n = 118 000). To evaluate the interplay of the metabolome and the gut microbiome in the pathogenesis of depression, metabolic signatures of the gut microbiome were obtained from a 2019 study performed in Dutch cohorts. Data were analyzed from March to December 2021. Main outcomes and measures: Outcomes were lifetime and recurrent MDD, with 249 metabolites profiled with nuclear magnetic resonance spectroscopy with the Nightingale platform. Results: The study included 6811 individuals with lifetime MDD compared with 51 446 control individuals and 4370 individuals with recurrent MDD compared with 62 508 control individuals. Individuals with lifetime MDD were younger (median [IQR] age, 56 [49-62] years vs 58 [51-64] years) and more often female (4447 [65%] vs 2364 [35%]) than control individuals. Metabolic signatures of MDD consisted of 124 metabolites spanning the energy and lipid metabolism pathways. Novel findings included 49 metabolites, including those involved in the tricarboxylic acid cycle (ie, citrate and pyruvate). Citrate was significantly decreased (β [SE], -0.07 [0.02]; FDR = 4 × 10-04) and pyruvate was significantly increased (β [SE], 0.04 [0.02]; FDR = 0.02) in individuals with MDD. Changes observed in these metabolites, particularly lipoproteins, were consistent with the differential composition of gut microbiota belonging to the order Clostridiales and the phyla Proteobacteria/Pseudomonadota and Bacteroidetes/Bacteroidota. Mendelian randomization suggested that fatty acids and intermediate and very large density lipoproteins changed in association with the disease process but high-density lipoproteins and the metabolites in the tricarboxylic acid cycle did not. Conclusions and relevance: The study findings showed that energy metabolism was disturbed in individuals with MDD and that the interplay of the gut microbiome and blood metabolome may play a role in lipid metabolism in individuals with MDD.
MeSH term(s)	Humans ; Female ; Middle Aged ; Gastrointestinal Microbiome/genetics ; Depressive Disorder, Major/genetics ; Depressive Disorder, Major/metabolism ; Genome-Wide Association Study ; Cohort Studies ; Metabolome ; Citrates/pharmacology ; Pyruvates/pharmacology
Chemical Substances	Citrates ; Pyruvates
Language	English
Publishing date	2023-06-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2701203-7
ISSN	2168-6238 ; 2168-622X
ISSN (online)	2168-6238
ISSN	2168-622X
DOI	10.1001/jamapsychiatry.2023.0685
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Article ; Online: Linkage analysis and whole exome sequencing identify a novel candidate gene in a Dutch multiple sclerosis family.

Mescheriakova, Julia Y / Verkerk, Annemieke Jmh / Amin, Najaf / Uitterlinden, André G / van Duijn, Cornelia M / Hintzen, Rogier Q

Multiple sclerosis (Houndmills, Basingstoke, England)

2018 Volume 25, Issue 7, Page(s) 909–917

Abstract: Background: Multiple sclerosis (MS) is a complex disease resulting from the joint effect of many genes. It has been speculated that rare variants might explain part of the missing heritability of MS.: Objective: To identify rare coding genetic ... ...

Abstract	Background: Multiple sclerosis (MS) is a complex disease resulting from the joint effect of many genes. It has been speculated that rare variants might explain part of the missing heritability of MS. Objective: To identify rare coding genetic variants by analyzing a large MS pedigree with 11 affected individuals in several generations. Methods: Genome-wide linkage screen and whole exome sequencing (WES) were performed to identify novel coding variants in the shared region(s) and in the known 110 MS risk loci. The candidate variants were then assessed in 591 MS patients and 3169 controls. Results: Suggestive evidence for linkage was obtained to 7q11.22-q11.23. In WES data, a rare missense variant p.R183C in FKBP6 was identified that segregated with the disease in this family. The minor allele frequency was higher in an independent cohort of MS patients than in healthy controls (1.27% vs 0.95%), but not significant (odds ratio (OR) = 1.33 (95% confidence interval (CI): 0.8-2.4), p = 0.31). Conclusion: The rare missense variant in FKBP6 was identified in a large Dutch MS family segregating with the disease. This association to MS was not found in an independent MS cohort. Overall, genome-wide studies in larger cohorts are needed to adequately investigate the role of rare variants in MS risk.
MeSH term(s)	Adult ; Aged ; Female ; Genetic Linkage ; Humans ; Male ; Middle Aged ; Multiple Sclerosis/genetics ; Mutation, Missense ; Netherlands ; Pedigree ; Tacrolimus Binding Proteins/genetics ; Whole Exome Sequencing
Chemical Substances	FKBP6 protein, human ; Tacrolimus Binding Proteins (EC 5.2.1.-)
Language	English
Publishing date	2018-06-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1290669-4
ISSN	1477-0970 ; 1352-4585
ISSN (online)	1477-0970
ISSN	1352-4585
DOI	10.1177/1352458518777202
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Article ; Online: The effect of APOE and other common genetic variants on the onset of Alzheimer's disease and dementia: a community-based cohort study.

van der Lee, Sven J / Wolters, Frank J / Ikram, M Kamran / Hofman, Albert / Ikram, M Arfan / Amin, Najaf / van Duijn, Cornelia M

The Lancet. Neurology

2018 Volume 17, Issue 5, Page(s) 434–444

Abstract: Background: Alzheimer's disease is one of the most heritable diseases in elderly people and the most common type of dementia. In addition to the major genetic determinant of Alzheimer's disease, the APOE gene, 23 genetic variants have been associated ... ...

Abstract	Background: Alzheimer's disease is one of the most heritable diseases in elderly people and the most common type of dementia. In addition to the major genetic determinant of Alzheimer's disease, the APOE gene, 23 genetic variants have been associated with the disease. We assessed the effects of these variants and APOE on cumulative risk and age at onset of Alzheimer's disease and all-cause dementia. Methods: We studied incident dementia in cognitively healthy participants (aged >45 years) from the community-based Rotterdam Study, an ongoing prospective cohort study based in Rotterdam, the Netherlands, focusing on neurological, cardiovascular, endocrine, and ophthalmological disorders, and other diseases in elderly people. The Rotterdam Study comprises participants in three baseline cohorts (initiated in 1990, 2000, and 2006), who are re-invited to the research centre every 3-4 years, and continuously monitored by records from general practitioners and medical specialists. Cumulative incidence curves up to age 100 years were calculated for Alzheimer's disease and dementia, taking into account mortality as a competing event. These risk curves were stratified by APOE genotypes, tertiles of a weighted genetic risk score (GRS) of 23 Alzheimer's disease-associated genetic variants, and parental history of dementia. Findings: 12 255 of 14 926 participants (58·5% women) from the Rotterdam Study were included in this study. During a median follow-up of 11·0 years (IQR 4·9-15·9; 133 123 person years), 1609 participants developed dementia, of whom 1262 (78%) were classified as having Alzheimer's disease; 3310 people died of causes other than dementia. Both APOE and the GRS significantly modified the risks of Alzheimer's disease and dementia. There was evidence for a significant interaction between APOE genotypes and the GRS for the association with Alzheimer's disease (p=0·03) and dementia (p=0·04); the risk for carriers homozygous for APOE ε4 was modified most by the GRS. In carriers homozygous for APOE ε4, the difference between the high-risk tertile and the low-risk tertile by age 85 years was 27·0% for Alzheimer's disease (p=8·5 × 10 Interpretation: Common variants with small individual effects jointly modify the risk and age at onset of Alzheimer's disease and dementia, particularly in APOE ε4 carriers. These findings highlight the potential of common variants in determining Alzheimer's disease risk. Funding: None.
MeSH term(s)	Age of Onset ; Aged ; Aged, 80 and over ; Alzheimer Disease/epidemiology ; Alzheimer Disease/genetics ; Apolipoproteins E/genetics ; Cohort Studies ; Dementia/epidemiology ; Dementia/genetics ; Female ; Humans ; Male ; Middle Aged ; Netherlands/epidemiology ; Risk Assessment/statistics & numerical data
Chemical Substances	ApoE protein, human ; Apolipoproteins E
Language	English
Publishing date	2018-03-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2079704-7
ISSN	1474-4465 ; 1474-4422
ISSN (online)	1474-4465
ISSN	1474-4422
DOI	10.1016/S1474-4422(18)30053-X
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