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Jonasson, Inger
Publications (7 of 7) Show all publications
Ameur, A., Dahlberg, J., Olason, P., Vezzi, F., Karlsson, R., Martin, M., . . . Gyllensten, U. B. (2017). SweGen: a whole-genome data resource of genetic variability in a cross-section of the Swedish population. European Journal of Human Genetics, 25(11), 1253-1260
Open this publication in new window or tab >>SweGen: a whole-genome data resource of genetic variability in a cross-section of the Swedish population
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2017 (English)In: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 25, no 11, p. 1253-1260Article in journal (Refereed) Published
Abstract [en]

Here we describe the SweGen data set, a comprehensive map of genetic variation in the Swedish population. These data represent a basic resource for clinical genetics laboratories as well as for sequencing-based association studies by providing information on genetic variant frequencies in a cohort that is well matched to national patient cohorts. To select samples for this study, we first examined the genetic structure of the Swedish population using high-density SNP-array data from a nation-wide cohort of over 10 000 Swedish-born individuals included in the Swedish Twin Registry. A total of 1000 individuals, reflecting a cross-section of the population and capturing the main genetic structure, were selected for whole-genome sequencing. Analysis pipelines were developed for automated alignment, variant calling and quality control of the sequencing data. This resulted in a genome-wide collection of aggregated variant frequencies in the Swedish population that we have made available to the scientific community through the website https://swefreq.nbis.se. A total of 29.2 million single-nucleotide variants and 3.8 million indels were detected in the 1000 samples, with 9.9 million of these variants not present in current databases. Each sample contributed with an average of 7199 individual-specific variants. In addition, an average of 8645 larger structural variants (SVs) were detected per individual, and we demonstrate that the population frequencies of these SVs can be used for efficient filtering analyses. Finally, our results show that the genetic diversity within Sweden is substantial compared with the diversity among continental European populations, underscoring the relevance of establishing a local reference data set.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2017
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-337314 (URN)10.1038/ejhg.2017.130 (DOI)000412823800012 ()28832569 (PubMedID)
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscienceKnut and Alice Wallenberg Foundation, 2014.0272Swedish Research CouncilSwedish National Infrastructure for Computing (SNIC), sens2016003EU, European Research Council, 282330
Available from: 2018-01-08 Created: 2018-01-08 Last updated: 2018-08-27Bibliographically approved
Lopes, F., Barbosa, M., Ameur, A., Soares, G., de Sa, J., Dias, A. I., . . . Maciel, P. (2016). Identification of novel genetic causes of Rett syndrome-like phenotypes. Journal of Medical Genetics, 53(3), 190-199
Open this publication in new window or tab >>Identification of novel genetic causes of Rett syndrome-like phenotypes
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2016 (English)In: Journal of Medical Genetics, ISSN 0022-2593, E-ISSN 1468-6244, Vol. 53, no 3, p. 190-199Article in journal (Refereed) Published
Abstract [en]

Background The aim of this work was to identify new genetic causes of Rett-like phenotypes using array comparative genomic hybridisation and a whole exome sequencing approach. Methods and results We studied a cohort of 19 Portuguese patients (16 girls, 3 boys) with a clinical presentation significantly overlapping Rett syndrome (RTT). Genetic analysis included filtering of the single nucleotide variants and indels with preference for de novo, homozygous/compound heterozygous, or maternally inherited X linked variants. Examination by MRI and muscle biopsies was also performed. Pathogenic genomic imbalances were found in two patients (10.5%): an 18q21.2 deletion encompassing four exons of the TCF4 gene and a mosaic UPD of chromosome 3. Variants in genes previously implicated in neurodevelopmental disorders (NDD) were identified in six patients (32%): de novo variants in EEF1A2, STXBP1 and ZNF238 were found in three patients, maternally inherited X linked variants in SLC35A2, ZFX and SHROOM4 were detected in two male patients and one homozygous variant in EIF2B2 was detected in one patient. Variants were also detected in five novel NDD candidate genes (26%): we identified de novo variants in the RHOBTB2, SMARCA1 and GABBR2 genes; a homozygous variant in EIF4G1; compound heterozygous variant in HTT. Conclusions Network analysis reveals that these genes interact by means of protein interactions with each other and with the known RTT genes. These findings expand the phenotypical spectrum of previously known NDD genes to encompass RTT-like clinical presentations and identify new candidate genes for RTT-like phenotypes.

Keywords
Rett syndrome, Epilepsy, Whole exome sequencing, Intellectual disability
National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-282471 (URN)10.1136/jmedgenet-2015-103568 (DOI)000371329600006 ()26740508 (PubMedID)
Available from: 2016-04-05 Created: 2016-04-05 Last updated: 2018-01-10Bibliographically approved
Lopes, F., Barbosa, M., Temudo, T., de Sa, J., Dias, A. I., Oliveira, G., . . . Maciel, P. (2015). Identification of novel genetic causes of Rett syndrome-like phenotypes by whole exome sequencing. Paper presented at Joint Meeting of the 20th Biennial Meeting of the International-Society-for-Developmental-Neuroscience / 5th Annual NeuroDevNet Brain Development Conference, JUL 19-24, 2014, Montreal, CANADA. International Journal of Developmental Neuroscience, 47, 99-99
Open this publication in new window or tab >>Identification of novel genetic causes of Rett syndrome-like phenotypes by whole exome sequencing
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2015 (English)In: International Journal of Developmental Neuroscience, ISSN 0736-5748, E-ISSN 1873-474X, Vol. 47, p. 99-99Article in journal, Meeting abstract (Other academic) Published
National Category
Medical Genetics Neurosciences
Identifiers
urn:nbn:se:uu:diva-279217 (URN)10.1016/j.ijdevneu.2015.04.269 (DOI)000366534600259 ()26531593 (PubMedID)
Conference
Joint Meeting of the 20th Biennial Meeting of the International-Society-for-Developmental-Neuroscience / 5th Annual NeuroDevNet Brain Development Conference, JUL 19-24, 2014, Montreal, CANADA
Available from: 2016-03-02 Created: 2016-02-29 Last updated: 2018-01-10Bibliographically approved
Gyllensten, U., Johansson, Å., Enroth, S. & Jonasson, I. (2013). Assessing The Effects Of Climate Change On Health And Lifestyle In Sub-Arctic Areas In Sweden - The Northern Sweden Population Health Study. Paper presented at 15th International Congress on Circumpolar Health; August 5–10, 2012; Fairbanks, Alaska, USA. International Journal of Circumpolar Health, 72(Suppl. 1), 516-517
Open this publication in new window or tab >>Assessing The Effects Of Climate Change On Health And Lifestyle In Sub-Arctic Areas In Sweden - The Northern Sweden Population Health Study
2013 (English)In: International Journal of Circumpolar Health, ISSN 1239-9736, E-ISSN 2242-3982, Vol. 72, no Suppl. 1, p. 516-517Article in journal, Meeting abstract (Other academic) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-211621 (URN)000325721900165 ()
Conference
15th International Congress on Circumpolar Health; August 5–10, 2012; Fairbanks, Alaska, USA
Available from: 2013-11-27 Created: 2013-11-27 Last updated: 2018-07-06Bibliographically approved
Demirkan, A., van Duijn, C. M., Ugocsai, P., Isaacs, A., Pramstaller, P. P., Liebisch, G., . . . Schmitz, G. (2012). Genome-Wide Association Study Identifies Novel Loci Associated with Circulating Phospho- and Sphingolipid Concentrations. PLoS Genetics, 8(2), e1002490
Open this publication in new window or tab >>Genome-Wide Association Study Identifies Novel Loci Associated with Circulating Phospho- and Sphingolipid Concentrations
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2012 (English)In: PLoS Genetics, ISSN 1553-7390, Vol. 8, no 2, p. e1002490-Article in journal (Refereed) Published
Abstract [en]

Phospho- and sphingolipids are crucial cellular and intracellular compounds. These lipids are required for active transport, a number of enzymatic processes, membrane formation, and cell signalling. Disruption of their metabolism leads to several diseases, with diverse neurological, psychiatric, and metabolic consequences. A large number of phospholipid and sphingolipid species can be detected and measured in human plasma. We conducted a meta-analysis of five European family-based genome-wide association studies (N = 4034) on plasma levels of 24 sphingomyelins (SPM), 9 ceramides (CER), 57 phosphatidylcholines (PC), 20 lysophosphatidylcholines (LPC), 27 phosphatidylethanolamines (PE), and 16 PE-based plasmalogens (PLPE), as well as their proportions in each major class. This effort yielded 25 genome-wide significant loci for phospholipids (smallest P-value = 9.88 x 10(-204)) and 10 loci for sphingolipids (smallest P-value = 3.10 x 10(-57)). After a correction for multiple comparisons (P-value, 2.2 x 10(-9)), we observed four novel loci significantly associated with phospholipids (PAQR9, AGPAT1, PKD2L1, PDXDC1) and two with sphingolipids (PLD2 and APOE) explaining up to 3.1% of the variance. Further analysis of the top findings with respect to within class molar proportions uncovered three additional loci for phospholipids (PNLIPRP2, PCDH20, and ABDH3) suggesting their involvement in either fatty acid elongation/saturation processes or fatty acid specific turnover mechanisms. Among those, 14 loci (KCNH7, AGPAT1, PNLIPRP2, SYT9, FADS1-2-3, DLG2, APOA1, ELOVL2, CDK17, LIPC, PDXDC1, PLD2, LASS4, and APOE) mapped into the glycerophospholipid and 12 loci (ILKAP, ITGA9, AGPAT1, FADS1-2-3, APOA1, PCDH20, LIPC, PDXDC1, SGPP1, APOE, LASS4, and PLD2) to the sphingolipid pathways. In large meta-analyses, associations between FADS1-2-3 and carotid intima media thickness, AGPAT1 and type 2 diabetes, and APOA1 and coronary artery disease were observed. In conclusion, our study identified nine novel phospho- and sphingolipid loci, substantially increasing our knowledge of the genetic basis for these traits.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-171674 (URN)10.1371/journal.pgen.1002490 (DOI)000300725500014 ()
Available from: 2012-03-26 Created: 2012-03-25 Last updated: 2018-07-06Bibliographically approved
Johansson, Å., Marroni, F., Hayward, C., Franklin, C. S., Kirichenko, A. V., Jonasson, I., . . . Gyllensten, U. (2009). Common variants in the JAZF1 gene associated with height identified by linkage and genome-wide association analysis. Human Molecular Genetics, 18(2), 373-380
Open this publication in new window or tab >>Common variants in the JAZF1 gene associated with height identified by linkage and genome-wide association analysis
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2009 (English)In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 18, no 2, p. 373-380Article in journal (Refereed) Published
Abstract [en]

Genes for height has gained interest for decades, but only recently have candidate genes started to be identified. We have performed linkage analysis and genome-wide association for height in approximately 4,000 individuals from five European populations. A total of 5 chromosomal regions showed suggestive linkage and in one of these regions, two SNPs (rs849140 and rs1635852) were associated with height (nominal p=7.0 x 10(-8) and p=9.6 x 10(-7) respectively). In total, five SNPs across the genome showed an association with height that reached the threshold of genome-wide significance (nominal p<1.6 x 10(-7)). The association with height was replicated for two SNPs (rs1635852 and rs849140) using three independent studies (N=31,077, N=1,268 and N=5,746) with overall meta p-values of 9.4x10(-10) and 5.3x10(-8). These SNPs are located in the JAZF1 gene, which has recently been associated with type II diabetes, prostate and endometrial cancer. JAZF1 is a transcriptional repressor of NR2C2, which results in low IGF1 serum concentrations, perinatal and early postnatal hypoglycaemia and growth retardation when knocked-out in mice. Both the linkage and association analyses independently identified the JAZF1 region affecting human height. We have demonstrated, through replication in additional independent populations, the consistency of the effect of the JAZF1 SNPs on height. Since this gene also has a key function in the metabolism of growth, JAZF1 represents one of the strongest candidates influencing human height so far identified.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-86906 (URN)10.1093/hmg/ddn350 (DOI)000261897500016 ()18952825 (PubMedID)
Available from: 2009-01-07 Created: 2008-12-09 Last updated: 2018-07-06Bibliographically approved
Aulchenko, Y. S., Ripatti, S., Lindqvist, I., Boomsma, D., Heid, I. M., Pramstaller, P. P., . . . Peltonen, L. (2009). Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. Nature Genetics, 41(1), 47-55
Open this publication in new window or tab >>Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts
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2009 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 41, no 1, p. 47-55Article in journal (Refereed) Published
Abstract [en]

Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P < 5 x 10(-8)), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 x 10(-11); LDL, P = 2.6 x 10(-10)), TMEM57 (TC, P = 5.4 x 10(-10)), CTCF-PRMT8 region (HDL, P = 8.3 x 10(-16)), DNAH11 (LDL, P = 6.1 x 10(-9)), FADS3-FADS2 (TC, P = 1.5 x 10(-10); LDL, P = 4.4 x 10(-13)) and MADD-FOLH1 region (HDL, P = 6 x 10(-11)). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.

National Category
Medical and Health Sciences
Research subject
Genetics
Identifiers
urn:nbn:se:uu:diva-86913 (URN)10.1038/ng.269 (DOI)000262085300015 ()19060911 (PubMedID)
Available from: 2009-01-07 Created: 2008-12-09 Last updated: 2018-07-06Bibliographically approved
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