Whole-genome sequencing identifies variants in ANK1, LRRN1, HAS1, and other genes and regulatory regions for stroke in type 1 diabetes.

Humans Diabetes Mellitus, Type 1 / genetics Whole Genome Sequencing Ankyrins / genetics Stroke / genetics Genome-Wide Association Study Genetic Predisposition to Disease Male Female Polymorphism, Single Nucleotide Membrane Proteins / genetics Adult Middle Aged Regulatory Sequences, Nucleic Acid / genetics

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
11 Jun 2024
Historique:
received: 25 09 2023
accepted: 10 05 2024
medline: 12 6 2024
pubmed: 12 6 2024
entrez: 11 6 2024
Statut: epublish

Résumé

Individuals with type 1 diabetes (T1D) carry a markedly increased risk of stroke, with distinct clinical and neuroimaging characteristics as compared to those without diabetes. Using whole-exome or whole-genome sequencing of 1,051 individuals with T1D, we aimed to find rare and low-frequency genomic variants associated with stroke in T1D. We analysed the genome comprehensively with single-variant analyses, gene aggregate analyses, and aggregate analyses on genomic windows, enhancers and promoters. In addition, we attempted replication in T1D using a genome-wide association study (N = 3,945) and direct genotyping (N = 3,263), and in the general population from the large-scale population-wide FinnGen project and UK Biobank summary statistics. We identified a rare missense variant on SREBF1 exome-wide significantly associated with stroke (rs114001633, p.Pro227Leu, p-value = 7.30 × 10

Identifiants

DOI: 10.1038/s41598-024-61840-7 PMID: 38862513
pubmed: 38862513
doi: 10.1038/s41598-024-61840-7
pii: 10.1038/s41598-024-61840-7
doi:

Substances chimiques

Ankyrins 0
ANK1 protein, human 0
Membrane Proteins 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

13453

Subventions

Organisme : Wellcome Trust
ID : 220027
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 220027
Pays : United Kingdom
Organisme : Helsinki University Central Hospital Research Funds
ID : TYH2018207
Organisme : Novo Nordisk Foundation
ID : NNFOC0013659
Organisme : Academy of Finland
ID : 316664
Organisme : Academy of Finland
ID : 299200
Organisme : Novo Nordisk Fonden
ID : NNF23OC0082732

Investigateurs

Anni A Antikainen (AA)
Jani K Haukka (JK)
Anmol Kumar (A)
Anna Syreeni (A)
Stefanie Hägg-Holmberg (S)
Anni Ylinen (A)
Jukka Putaala (J)
Lena M Thorn (LM)
Valma Harjutsalo (V)
Per-Henrik Groop (PH)
Niina Sandholm (N)

Informations de copyright

© 2024. The Author(s).

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Auteurs

Anni A Antikainen (AA)

Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Jani K Haukka (JK)

Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Anmol Kumar (A)

Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Anna Syreeni (A)

Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Stefanie Hägg-Holmberg (S)

Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Anni Ylinen (A)

Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Elina Kilpeläinen (E)

Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.

Anastasia Kytölä (A)

Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.

Aarno Palotie (A)

Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
Analytic and Translational Genetics Unit, Department of Medicine, Department of Neurology and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
The Stanley Center for Psychiatric Research and Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Jukka Putaala (J)

Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Lena M Thorn (LM)

Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Valma Harjutsalo (V)

Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Per-Henrik Groop (PH)

Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland. per-henrik.groop@helsinki.fi.
Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. per-henrik.groop@helsinki.fi.
Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland. per-henrik.groop@helsinki.fi.
Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC, Australia. per-henrik.groop@helsinki.fi.

Niina Sandholm (N)

Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland. niina.sandholm@helsinki.fi.
Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. niina.sandholm@helsinki.fi.
Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland. niina.sandholm@helsinki.fi.

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questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Whole-genome sequencing identifies variants in...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Diabète de type 1 › Whole-genome sequencing identifies variants in...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ADN › Séquençage du génome entier › Whole-genome sequencing identifies variants in...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Ankyrines › Whole-genome sequencing identifies variants in...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Angiopathies intracrâniennes › Accident vasculaire cérébral › Whole-genome sequencing identifies variants in...
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questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Whole-genome sequencing identifies variants in...
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