A Novel Genetic Marker for the C9orf72 Repeat Expansion in the Finnish Population
C9orf72 repeat expansion (C9exp) is the most common genetic cause underlying frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). However, detection of the C9exp requires elaborative methods. Identification of C9exp carriers from genotyped cohorts could be facilitated by...
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| Veröffentlicht in: | Journal of Alzheimer's disease 2021-01, Vol.83 (3), p.1325-1332 |
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| creator | Rostalski, Hannah Korhonen, Ville Kuulasmaa, Teemu Solje, Eino Krüger, Johanna Gen, Finn Kaivola, Karri Eide, Per Kristian Lambert, Jean-Charles Julkunen, Valtteri Tienari, Pentti J Remes, Anne M Leinonen, Ville Hiltunen, Mikko Haapasalo, Annakaisa |
| description | C9orf72 repeat expansion (C9exp) is the most common genetic cause underlying frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). However, detection of the C9exp requires elaborative methods.
Identification of C9exp carriers from genotyped cohorts could be facilitated by using single nucleotide polymorphisms (SNPs) as markers for the C9exp.
We elucidated the potential of the previously described Finnish risk haplotype, defined by the SNP rs3849942, to identify potential C9exp carriers among 218,792 Finns using the FinnGen database. The haplotype approach was first tested in an idiopathic normal pressure hydrocephalus (iNPH) patient cohort (European Alzheimer's Disease DNA BioBank) containing C9exp carriers by comparing intermediate (15-30) and full-length (> 60 repeats) C9exp carriers (n = 41) to C9exp negative patients ( |
| doi_str_mv | 10.3233/JAD-210599 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_3HK</sourceid><recordid>TN_cdi_cristin_nora_10852_90980</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2577056814</sourcerecordid><originalsourceid>FETCH-LOGICAL-c409t-1af2720795f6c8907f04088200c906ec0154c8b706450536f8445345cefc8f763</originalsourceid><addsrcrecordid>eNpd0UtvVCEUB3BiNLZWN34AJXGjJlcPb1hOxj404zO6JhQhQ70Dt3Bvo99e6rRduIJwfjmckz9CTwm8YZSxtx9W7wZKQBhzDx0SrcSgDej7_c60GqhW6gA9au0CABgY9RAdMM6M4kQeoq8r_KlchRGfhhzm5PFHV3-FimOpeN4GvDalRkXxtzAFN-Pj35PLLZWMU_5XP0k5p7bFX8q0jG7ulcfoQXRjC09uziP04-T4-_ps2Hw-fb9ebQbPwcwDcZEqCsqIKH2fV0XgoDUF8AZk8EAE9_pcgeQCBJNRcy4YFz5Er6OS7Ai92vfdutFONe1c_WOLS_ZstbHXb8CpUsawK9Lt8731NbU5ZZtLdZaAFtQaMBq6eLkXUy2XS2iz3aXmwzi6HMrSLBWSGCq5UZ2--I9elKXmvmtXSoGQmvCuXt9-WVqrId7NSMBex2Z7bHYfW8fPblou57vw847e5sT-AnTmi6c</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2577056814</pqid></control><display><type>article</type><title>A Novel Genetic Marker for the C9orf72 Repeat Expansion in the Finnish Population</title><source>NORA - Norwegian Open Research Archives</source><creator>Rostalski, Hannah ; Korhonen, Ville ; Kuulasmaa, Teemu ; Solje, Eino ; Krüger, Johanna ; Gen, Finn ; Kaivola, Karri ; Eide, Per Kristian ; Lambert, Jean-Charles ; Julkunen, Valtteri ; Tienari, Pentti J ; Remes, Anne M ; Leinonen, Ville ; Hiltunen, Mikko ; Haapasalo, Annakaisa</creator><creatorcontrib>Rostalski, Hannah ; Korhonen, Ville ; Kuulasmaa, Teemu ; Solje, Eino ; Krüger, Johanna ; Gen, Finn ; Kaivola, Karri ; Eide, Per Kristian ; Lambert, Jean-Charles ; Julkunen, Valtteri ; Tienari, Pentti J ; Remes, Anne M ; Leinonen, Ville ; Hiltunen, Mikko ; Haapasalo, Annakaisa</creatorcontrib><description>C9orf72 repeat expansion (C9exp) is the most common genetic cause underlying frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). However, detection of the C9exp requires elaborative methods.
Identification of C9exp carriers from genotyped cohorts could be facilitated by using single nucleotide polymorphisms (SNPs) as markers for the C9exp.
We elucidated the potential of the previously described Finnish risk haplotype, defined by the SNP rs3849942, to identify potential C9exp carriers among 218,792 Finns using the FinnGen database. The haplotype approach was first tested in an idiopathic normal pressure hydrocephalus (iNPH) patient cohort (European Alzheimer's Disease DNA BioBank) containing C9exp carriers by comparing intermediate (15-30) and full-length (> 60 repeats) C9exp carriers (n = 41) to C9exp negative patients (< 15 repeats, n = 801).
In this analysis, rs3849942 was associated with carriership of C9exp (OR 8.44, p < 2×10-15), while the strongest association was found with rs139185008 (OR 39.4, p < 5×10-18). Unbiased analysis of rs139185008 in FinnGen showed the strongest association with FTLD (OR 4.38, 3×10-15) and motor neuron disease ALS (OR 5.19, 3×10-21). rs139185008 was the top SNP in all diseases (iNPH, FTLD, ALS), and further showed a strong association with ALS in the UK Biobank (p = 9.0×10-8).
Our findings suggest that rs139185008 is a useful marker to identify potential C9exp carriers in the genotyped cohorts and biobanks originating from Finland.</description><identifier>ISSN: 1387-2877</identifier><identifier>EISSN: 1875-8908</identifier><identifier>DOI: 10.3233/JAD-210599</identifier><identifier>PMID: 34397416</identifier><language>eng</language><publisher>Netherlands: IOS Press BV</publisher><subject>Aged ; Alzheimer's disease ; Amyotrophic lateral sclerosis ; Amyotrophic Lateral Sclerosis - genetics ; Biobanks ; C9orf72 Protein - genetics ; Cohort Studies ; Degeneration ; Deoxyribonucleic acid ; DNA ; Female ; Finland ; Frontotemporal dementia ; Frontotemporal Dementia - genetics ; Genetic Markers ; Genotype ; Haplotypes ; Heterozygote ; Humans ; Hydrocephalus ; Life Sciences ; Male ; Markers ; Middle Aged ; Motor neuron diseases ; Motor neurone disease ; Neurodegenerative diseases ; Nucleotides ; Polymorphism, Single Nucleotide ; Single-nucleotide polymorphism</subject><ispartof>Journal of Alzheimer's disease, 2021-01, Vol.83 (3), p.1325-1332</ispartof><rights>Copyright IOS Press BV 2021</rights><rights>info:eu-repo/semantics/openAccess</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c409t-1af2720795f6c8907f04088200c906ec0154c8b706450536f8445345cefc8f763</citedby><cites>FETCH-LOGICAL-c409t-1af2720795f6c8907f04088200c906ec0154c8b706450536f8445345cefc8f763</cites><orcidid>0000-0003-0829-7817</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,778,883,26550</link.rule.ids><linktorsrc>$$Uhttp://hdl.handle.net/10852/90980$$EView_record_in_NORA$$FView_record_in_$$GNORA$$Hfree_for_read</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34397416$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-04277993$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Rostalski, Hannah</creatorcontrib><creatorcontrib>Korhonen, Ville</creatorcontrib><creatorcontrib>Kuulasmaa, Teemu</creatorcontrib><creatorcontrib>Solje, Eino</creatorcontrib><creatorcontrib>Krüger, Johanna</creatorcontrib><creatorcontrib>Gen, Finn</creatorcontrib><creatorcontrib>Kaivola, Karri</creatorcontrib><creatorcontrib>Eide, Per Kristian</creatorcontrib><creatorcontrib>Lambert, Jean-Charles</creatorcontrib><creatorcontrib>Julkunen, Valtteri</creatorcontrib><creatorcontrib>Tienari, Pentti J</creatorcontrib><creatorcontrib>Remes, Anne M</creatorcontrib><creatorcontrib>Leinonen, Ville</creatorcontrib><creatorcontrib>Hiltunen, Mikko</creatorcontrib><creatorcontrib>Haapasalo, Annakaisa</creatorcontrib><title>A Novel Genetic Marker for the C9orf72 Repeat Expansion in the Finnish Population</title><title>Journal of Alzheimer's disease</title><addtitle>J Alzheimers Dis</addtitle><description>C9orf72 repeat expansion (C9exp) is the most common genetic cause underlying frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). However, detection of the C9exp requires elaborative methods.
Identification of C9exp carriers from genotyped cohorts could be facilitated by using single nucleotide polymorphisms (SNPs) as markers for the C9exp.
We elucidated the potential of the previously described Finnish risk haplotype, defined by the SNP rs3849942, to identify potential C9exp carriers among 218,792 Finns using the FinnGen database. The haplotype approach was first tested in an idiopathic normal pressure hydrocephalus (iNPH) patient cohort (European Alzheimer's Disease DNA BioBank) containing C9exp carriers by comparing intermediate (15-30) and full-length (> 60 repeats) C9exp carriers (n = 41) to C9exp negative patients (< 15 repeats, n = 801).
In this analysis, rs3849942 was associated with carriership of C9exp (OR 8.44, p < 2×10-15), while the strongest association was found with rs139185008 (OR 39.4, p < 5×10-18). Unbiased analysis of rs139185008 in FinnGen showed the strongest association with FTLD (OR 4.38, 3×10-15) and motor neuron disease ALS (OR 5.19, 3×10-21). rs139185008 was the top SNP in all diseases (iNPH, FTLD, ALS), and further showed a strong association with ALS in the UK Biobank (p = 9.0×10-8).
Our findings suggest that rs139185008 is a useful marker to identify potential C9exp carriers in the genotyped cohorts and biobanks originating from Finland.</description><subject>Aged</subject><subject>Alzheimer's disease</subject><subject>Amyotrophic lateral sclerosis</subject><subject>Amyotrophic Lateral Sclerosis - genetics</subject><subject>Biobanks</subject><subject>C9orf72 Protein - genetics</subject><subject>Cohort Studies</subject><subject>Degeneration</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Female</subject><subject>Finland</subject><subject>Frontotemporal dementia</subject><subject>Frontotemporal Dementia - genetics</subject><subject>Genetic Markers</subject><subject>Genotype</subject><subject>Haplotypes</subject><subject>Heterozygote</subject><subject>Humans</subject><subject>Hydrocephalus</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Markers</subject><subject>Middle Aged</subject><subject>Motor neuron diseases</subject><subject>Motor neurone disease</subject><subject>Neurodegenerative diseases</subject><subject>Nucleotides</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Single-nucleotide polymorphism</subject><issn>1387-2877</issn><issn>1875-8908</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>3HK</sourceid><recordid>eNpd0UtvVCEUB3BiNLZWN34AJXGjJlcPb1hOxj404zO6JhQhQ70Dt3Bvo99e6rRduIJwfjmckz9CTwm8YZSxtx9W7wZKQBhzDx0SrcSgDej7_c60GqhW6gA9au0CABgY9RAdMM6M4kQeoq8r_KlchRGfhhzm5PFHV3-FimOpeN4GvDalRkXxtzAFN-Pj35PLLZWMU_5XP0k5p7bFX8q0jG7ulcfoQXRjC09uziP04-T4-_ps2Hw-fb9ebQbPwcwDcZEqCsqIKH2fV0XgoDUF8AZk8EAE9_pcgeQCBJNRcy4YFz5Er6OS7Ai92vfdutFONe1c_WOLS_ZstbHXb8CpUsawK9Lt8731NbU5ZZtLdZaAFtQaMBq6eLkXUy2XS2iz3aXmwzi6HMrSLBWSGCq5UZ2--I9elKXmvmtXSoGQmvCuXt9-WVqrId7NSMBex2Z7bHYfW8fPblou57vw847e5sT-AnTmi6c</recordid><startdate>20210101</startdate><enddate>20210101</enddate><creator>Rostalski, Hannah</creator><creator>Korhonen, Ville</creator><creator>Kuulasmaa, Teemu</creator><creator>Solje, Eino</creator><creator>Krüger, Johanna</creator><creator>Gen, Finn</creator><creator>Kaivola, Karri</creator><creator>Eide, Per Kristian</creator><creator>Lambert, Jean-Charles</creator><creator>Julkunen, Valtteri</creator><creator>Tienari, Pentti J</creator><creator>Remes, Anne M</creator><creator>Leinonen, Ville</creator><creator>Hiltunen, Mikko</creator><creator>Haapasalo, Annakaisa</creator><general>IOS Press BV</general><general>IOS Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>3HK</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0003-0829-7817</orcidid></search><sort><creationdate>20210101</creationdate><title>A Novel Genetic Marker for the C9orf72 Repeat Expansion in the Finnish Population</title><author>Rostalski, Hannah ; Korhonen, Ville ; Kuulasmaa, Teemu ; Solje, Eino ; Krüger, Johanna ; Gen, Finn ; Kaivola, Karri ; Eide, Per Kristian ; Lambert, Jean-Charles ; Julkunen, Valtteri ; Tienari, Pentti J ; Remes, Anne M ; Leinonen, Ville ; Hiltunen, Mikko ; Haapasalo, Annakaisa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c409t-1af2720795f6c8907f04088200c906ec0154c8b706450536f8445345cefc8f763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Aged</topic><topic>Alzheimer's disease</topic><topic>Amyotrophic lateral sclerosis</topic><topic>Amyotrophic Lateral Sclerosis - genetics</topic><topic>Biobanks</topic><topic>C9orf72 Protein - genetics</topic><topic>Cohort Studies</topic><topic>Degeneration</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Female</topic><topic>Finland</topic><topic>Frontotemporal dementia</topic><topic>Frontotemporal Dementia - genetics</topic><topic>Genetic Markers</topic><topic>Genotype</topic><topic>Haplotypes</topic><topic>Heterozygote</topic><topic>Humans</topic><topic>Hydrocephalus</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Markers</topic><topic>Middle Aged</topic><topic>Motor neuron diseases</topic><topic>Motor neurone disease</topic><topic>Neurodegenerative diseases</topic><topic>Nucleotides</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Single-nucleotide polymorphism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rostalski, Hannah</creatorcontrib><creatorcontrib>Korhonen, Ville</creatorcontrib><creatorcontrib>Kuulasmaa, Teemu</creatorcontrib><creatorcontrib>Solje, Eino</creatorcontrib><creatorcontrib>Krüger, Johanna</creatorcontrib><creatorcontrib>Gen, Finn</creatorcontrib><creatorcontrib>Kaivola, Karri</creatorcontrib><creatorcontrib>Eide, Per Kristian</creatorcontrib><creatorcontrib>Lambert, Jean-Charles</creatorcontrib><creatorcontrib>Julkunen, Valtteri</creatorcontrib><creatorcontrib>Tienari, Pentti J</creatorcontrib><creatorcontrib>Remes, Anne M</creatorcontrib><creatorcontrib>Leinonen, Ville</creatorcontrib><creatorcontrib>Hiltunen, Mikko</creatorcontrib><creatorcontrib>Haapasalo, Annakaisa</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>NORA - Norwegian Open Research Archives</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Journal of Alzheimer's disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Rostalski, Hannah</au><au>Korhonen, Ville</au><au>Kuulasmaa, Teemu</au><au>Solje, Eino</au><au>Krüger, Johanna</au><au>Gen, Finn</au><au>Kaivola, Karri</au><au>Eide, Per Kristian</au><au>Lambert, Jean-Charles</au><au>Julkunen, Valtteri</au><au>Tienari, Pentti J</au><au>Remes, Anne M</au><au>Leinonen, Ville</au><au>Hiltunen, Mikko</au><au>Haapasalo, Annakaisa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Novel Genetic Marker for the C9orf72 Repeat Expansion in the Finnish Population</atitle><jtitle>Journal of Alzheimer's disease</jtitle><addtitle>J Alzheimers Dis</addtitle><date>2021-01-01</date><risdate>2021</risdate><volume>83</volume><issue>3</issue><spage>1325</spage><epage>1332</epage><pages>1325-1332</pages><issn>1387-2877</issn><eissn>1875-8908</eissn><abstract>C9orf72 repeat expansion (C9exp) is the most common genetic cause underlying frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). However, detection of the C9exp requires elaborative methods.
Identification of C9exp carriers from genotyped cohorts could be facilitated by using single nucleotide polymorphisms (SNPs) as markers for the C9exp.
We elucidated the potential of the previously described Finnish risk haplotype, defined by the SNP rs3849942, to identify potential C9exp carriers among 218,792 Finns using the FinnGen database. The haplotype approach was first tested in an idiopathic normal pressure hydrocephalus (iNPH) patient cohort (European Alzheimer's Disease DNA BioBank) containing C9exp carriers by comparing intermediate (15-30) and full-length (> 60 repeats) C9exp carriers (n = 41) to C9exp negative patients (< 15 repeats, n = 801).
In this analysis, rs3849942 was associated with carriership of C9exp (OR 8.44, p < 2×10-15), while the strongest association was found with rs139185008 (OR 39.4, p < 5×10-18). Unbiased analysis of rs139185008 in FinnGen showed the strongest association with FTLD (OR 4.38, 3×10-15) and motor neuron disease ALS (OR 5.19, 3×10-21). rs139185008 was the top SNP in all diseases (iNPH, FTLD, ALS), and further showed a strong association with ALS in the UK Biobank (p = 9.0×10-8).
Our findings suggest that rs139185008 is a useful marker to identify potential C9exp carriers in the genotyped cohorts and biobanks originating from Finland.</abstract><cop>Netherlands</cop><pub>IOS Press BV</pub><pmid>34397416</pmid><doi>10.3233/JAD-210599</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-0829-7817</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1387-2877 |
| ispartof | Journal of Alzheimer's disease, 2021-01, Vol.83 (3), p.1325-1332 |
| issn | 1387-2877 1875-8908 |
| language | eng |
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| source | NORA - Norwegian Open Research Archives |
| subjects | Aged Alzheimer's disease Amyotrophic lateral sclerosis Amyotrophic Lateral Sclerosis - genetics Biobanks C9orf72 Protein - genetics Cohort Studies Degeneration Deoxyribonucleic acid DNA Female Finland Frontotemporal dementia Frontotemporal Dementia - genetics Genetic Markers Genotype Haplotypes Heterozygote Humans Hydrocephalus Life Sciences Male Markers Middle Aged Motor neuron diseases Motor neurone disease Neurodegenerative diseases Nucleotides Polymorphism, Single Nucleotide Single-nucleotide polymorphism |
| title | A Novel Genetic Marker for the C9orf72 Repeat Expansion in the Finnish Population |
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