ORCID Profile
0000-0002-0867-4726
Current Organisations
Karolinska University Hospital
,
Healthcare Provision, Stockholm County
,
Karolinska Institutet
,
Centrum för Molekylär Medicin
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Publications
Locus for severity implicates CNS resilience in progression of multiple sclerosis
Publisher: Springer Science and Business Media LLC
Date: 28-06-2023
Publisher Correction: Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality
Publisher: Springer Science and Business Media LLC
Date: 03-07-2023
Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk
Publisher: Elsevier BV
Date: 11-2018
NR1H3 p.Arg415Gln Is Not Associated to Multiple Sclerosis Risk
Publisher: Elsevier BV
Date: 10-2016
Network-based multiple sclerosis pathway analysis with GWAS data from 15,000 cases and 30,000 controls.
Publisher: Elsevier BV
Date: 06-2013
A gene pathway analysis highlights the role of cellular adhesion molecules in multiple sclerosis susceptibility
Publisher: Springer Science and Business Media LLC
Date: 16-01-2014
DOI: 10.1038/GENE.2013.70
Abstract: Genome-wide association studies (GWASs) perform per-SNP association tests to identify variants involved in disease or trait susceptibility. However, such an approach is not powerful enough to unravel genes that are not in idually contributing to the disease/trait, but that may have a role in interaction with other genes as a group. Pathway analysis is an alternative way to highlight such group of genes. Using SNP association P-values from eight multiple sclerosis (MS) GWAS data sets, we performed a candidate pathway analysis for MS susceptibility by considering genes interacting in the cell adhesion molecule (CAMs) biological pathway using Cytoscape software. This network is a strong candidate, as it is involved in the crossing of the blood-brain barrier by the T cells, an early event in MS pathophysiology, and is used as an efficient therapeutic target. We drew up a list of 76 genes belonging to the CAM network. We highlighted 64 networks enriched with CAM genes with low P-values. Filtering by a percentage of CAM genes up to 50% and rejecting enriched signals mainly driven by transcription factors, we highlighted five networks associated with MS susceptibility. One of them, constituted of ITGAL, ICAM1 and ICAM3 genes, could be of interest to develop novel therapeutic targets.
Small noncoding RNA profiling across cellular and biofluid compartments and their implications for multiple sclerosis immunopathology
Publisher: Proceedings of the National Academy of Sciences
Date: 20-04-2021
Abstract: Dysregulation of microRNAs (miRNAs), a type of small noncoding RNAs (sncRNAs), has frequently been associated with multiple sclerosis (MS). However, most studies have focused on peripheral blood, and few investigated other classes of sncRNAs. To address this, we analyzed all classes of sncRNAs in matching peripheral blood mononuclear cells, plasma, cerebrospinal fluid (CSF) cells, and cell-free CSF from MS patients and controls. We demonstrate widespread alterations of small nuclear (snRNA)–derived RNAs, small nucleolar-derived RNAs (sdRNAs), transfer RNA–derived fragments, and miRNAs, particularly in CSF cells. The striking contrast between the periphery and central nervous system and between relapse and remission phases of disease highlights the importance of sncRNA-mediated mechanisms in MS, in particular alternative splicing and mRNA translation.
No evidence for shared genetic basis of common variants in multiple sclerosis and amyotrophic lateral sclerosis
Publisher: Oxford University Press (OUP)
Date: 13-11-2013
DOI: 10.1093/HMG/DDT574
Abstract: Genome-wide association studies have been successful in identifying common variants that influence the susceptibility to complex diseases. From these studies, it has emerged that there is substantial overlap in susceptibility loci between diseases. In line with those findings, we hypothesized that shared genetic pathways may exist between multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). While both diseases may have inflammatory and neurodegenerative features, epidemiological studies have indicated an increased co-occurrence within in iduals and families. To this purpose, we combined genome-wide data from 4088 MS patients, 3762 ALS patients and 12 030 healthy control in iduals in whom 5 440 446 single-nucleotide polymorphisms (SNPs) were successfully genotyped or imputed. We tested these SNPs for the excess association shared between MS and ALS and also explored whether polygenic models of SNPs below genome-wide significance could explain some of the observed trait variance between diseases. Genome-wide association meta-analysis of SNPs as well as polygenic analyses fails to provide evidence in favor of an overlap in genetic susceptibility between MS and ALS. Hence, our findings do not support a shared genetic background of common risk variants in MS and ALS.
Technological readiness and implementation of genomic‐driven precision medicine for complex diseases
Publisher: Wiley
Date: 02-07-2021
DOI: 10.1111/JOIM.13330
Abstract: The fields of human genetics and genomics have generated considerable knowledge about the mechanistic basis of many diseases. Genomic approaches to diagnosis, prognostication, prevention and treatment – genomic‐driven precision medicine (GDPM) – may help optimize medical practice. Here, we provide a comprehensive review of GDPM of complex diseases across major medical specialties. We focus on technological readiness: how rapidly a test can be implemented into health care. Although these areas of medicine are erse, key similarities exist across almost all areas. Many medical areas have, within their standards of care, at least one GDPM test for a genetic variant of strong effect that aids the identification/diagnosis of a more homogeneous subset within a larger disease group or identifies a subset with different therapeutic requirements. However, for almost all complex diseases, the majority of patients do not carry established single‐gene mutations with large effects. Thus, research is underway that seeks to determine the polygenic basis of many complex diseases. Nevertheless, most complex diseases are caused by the interplay of genetic, behavioural and environmental risk factors, which will likely necessitate models for prediction and diagnosis that incorporate genetic and non‐genetic data.
Genetic variants are major determinants of CSF antibody levels in multiple sclerosis
Publisher: Oxford University Press (OUP)
Date: 22-01-2015
DOI: 10.1093/BRAIN/AWU405
Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis
Publisher: Springer Science and Business Media LLC
Date: 29-09-2013
DOI: 10.1038/NG.2770
Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality
Publisher: Springer Science and Business Media LLC
Date: 10-06-2023
DOI: 10.1038/S41467-023-38951-2
Abstract: Genotypes causing pregnancy loss and perinatal mortality are depleted among living in iduals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with deficit of homozygosity among 1.52 million in iduals from six European populations. In this study, we identified 25 genes harboring protein-altering sequence variants with a strong deficit of homozygosity (10% or less of predicted homozygotes). Sequence variants in 12 of the genes cause Mendelian disease under a recessive mode of inheritance, two under a dominant mode, but variants in the remaining 11 have not been reported to cause disease. Sequence variants with a strong deficit of homozygosity are over-represented among genes essential for growth of human cell lines and genes orthologous to mouse genes known to affect viability. The function of these genes gives insight into the genetics of intrauterine lethality. We also identified 1077 genes with homozygous predicted loss-of-function genotypes not previously described, bringing the total set of genes completely knocked out in humans to 4785.
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
Publisher: Springer Science and Business Media LLC
Date: 08-2011
DOI: 10.1038/NATURE10251
DNA Methylation Signatures of Multiple Sclerosis Occur Independently of Known Genetic Risk and Are Primarily Attributed to B Cells and Monocytes
Publisher: MDPI AG
Date: 08-08-2023
Abstract: Epigenetic mechanisms can regulate how DNA is expressed independently of sequence and are known to be associated with various diseases. Among those epigenetic mechanisms, DNA methylation (DNAm) is influenced by genotype and the environment, making it an important molecular interface for studying disease etiology and progression. In this study, we examined the whole blood DNA methylation profiles of a large group of people with (pw) multiple sclerosis (MS) compared to those of controls. We reveal that methylation differences in pwMS occur independently of known genetic risk loci and show that they more strongly differentiate disease (AUC = 0.85, 95% CI 0.82–0.89, p = 1.22 × 10−29) than known genetic risk loci (AUC = 0.72, 95% CI: 0.66–0.76, p = 9.07 × 10−17). We also show that methylation differences in MS occur predominantly in B cells and monocytes and indicate the involvement of cell-specific biological pathways. Overall, this study comprehensively characterizes the immune cell-specific epigenetic architecture of MS.
Lack of support for association between the KIF1B rs10492972[C] variant and multiple sclerosis
Publisher: Springer Science and Business Media LLC
Date: 06-2010
DOI: 10.1038/NG0610-469
Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations
Publisher: Springer Science and Business Media LLC
Date: 20-07-2015
DOI: 10.1038/NG.3359
Multiple sclerosis risk loci and disease severity in 7,125 individuals from 10 studies
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2016
Genetic pleiotropy between multiple sclerosis and schizophrenia but not bipolar disorder: differential involvement of immune-related gene loci
Publisher: Springer Science and Business Media LLC
Date: 28-01-2014
DOI: 10.1038/MP.2013.195
Related Organisations
University Of Cambridge
Location: United Kingdom of Great Britain and Northern Ireland
Related Funding Activities
No related grants have been discovered for Ingrid Kockum.