Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci
Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer (CRC), but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 CRC c...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Wiley
2017
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| _version_ | 1797102086214647808 |
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| author | Tanskanen, T van den Berg, L Välimäki, N Aavikko, M Ness-Jensen, E Hveem, K Wettergren, Y Lindskog, E Tõnisson, N Metspalu, A Silander, K Orlando, G Law, PJ Tuupanen, S Gylfe, AE Hänninen, UA Cajuso, T Kondelin, J Sarin, AP Pukkala, E Jousilahti, P Salomaa, V Ripatti, S Palotie, A Järvinen, H Renkonen-Sinisalo, L Lepistö, A Böhm, J Mecklin, JP Al-Tassan, NA Palles, C Martin, L Barclay, E Tenesa, A Farrington, SM Timofeeva, MN Meyer, BF Wakil, SM Campbell, H Smith, CG Idziaszczyk, S Maughan, TS Kaplan, R Kerr, R Kerr, D Buchanan, DD Win, AK Hopper, J Jenkins, MA Newcomb, PA Gallinger, S Conti, D Schumacher, FR Casey, G Cheadle, JP Dunlop, MG Tomlinson, IP Houlston, RS Palin, K Aaltonen, LA |
| author_facet | Tanskanen, T van den Berg, L Välimäki, N Aavikko, M Ness-Jensen, E Hveem, K Wettergren, Y Lindskog, E Tõnisson, N Metspalu, A Silander, K Orlando, G Law, PJ Tuupanen, S Gylfe, AE Hänninen, UA Cajuso, T Kondelin, J Sarin, AP Pukkala, E Jousilahti, P Salomaa, V Ripatti, S Palotie, A Järvinen, H Renkonen-Sinisalo, L Lepistö, A Böhm, J Mecklin, JP Al-Tassan, NA Palles, C Martin, L Barclay, E Tenesa, A Farrington, SM Timofeeva, MN Meyer, BF Wakil, SM Campbell, H Smith, CG Idziaszczyk, S Maughan, TS Kaplan, R Kerr, R Kerr, D Buchanan, DD Win, AK Hopper, J Jenkins, MA Newcomb, PA Gallinger, S Conti, D Schumacher, FR Casey, G Cheadle, JP Dunlop, MG Tomlinson, IP Houlston, RS Palin, K Aaltonen, LA |
| author_sort | Tanskanen, T |
| collection | OXFORD |
| description | Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer (CRC), but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 CRC cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism (SNP) rs992157 (2q35) and CRC was independently replicated (p = 2.08 × 10-4 ; OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p = 1.50 × 10-9 ; OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3 and 20q13.33 were associated with CRC in the Finnish population (false discovery rate < 0.1), but new risk loci were not found. These results replicate the effects of multiple loci on the risk of CRC and identify shared risk alleles between the Finnish population isolate and outbred populations. |
| first_indexed | 2024-03-07T06:00:53Z |
| format | Journal article |
| id | oxford-uuid:ec25be31-a554-4398-aa01-3ec925ad3a58 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:00:53Z |
| publishDate | 2017 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:ec25be31-a554-4398-aa01-3ec925ad3a582022-03-27T11:15:44ZGenome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk lociJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ec25be31-a554-4398-aa01-3ec925ad3a58EnglishSymplectic Elements at OxfordWiley2017Tanskanen, Tvan den Berg, LVälimäki, NAavikko, MNess-Jensen, EHveem, KWettergren, YLindskog, ETõnisson, NMetspalu, ASilander, KOrlando, GLaw, PJTuupanen, SGylfe, AEHänninen, UACajuso, TKondelin, JSarin, APPukkala, EJousilahti, PSalomaa, VRipatti, SPalotie, AJärvinen, HRenkonen-Sinisalo, LLepistö, ABöhm, JMecklin, JPAl-Tassan, NAPalles, CMartin, LBarclay, ETenesa, AFarrington, SMTimofeeva, MNMeyer, BFWakil, SMCampbell, HSmith, CGIdziaszczyk, SMaughan, TSKaplan, RKerr, RKerr, DBuchanan, DDWin, AKHopper, JJenkins, MANewcomb, PAGallinger, SConti, DSchumacher, FRCasey, GCheadle, JPDunlop, MGTomlinson, IPHoulston, RSPalin, KAaltonen, LAGenome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer (CRC), but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 CRC cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism (SNP) rs992157 (2q35) and CRC was independently replicated (p = 2.08 × 10-4 ; OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p = 1.50 × 10-9 ; OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3 and 20q13.33 were associated with CRC in the Finnish population (false discovery rate < 0.1), but new risk loci were not found. These results replicate the effects of multiple loci on the risk of CRC and identify shared risk alleles between the Finnish population isolate and outbred populations. |
| spellingShingle | Tanskanen, T van den Berg, L Välimäki, N Aavikko, M Ness-Jensen, E Hveem, K Wettergren, Y Lindskog, E Tõnisson, N Metspalu, A Silander, K Orlando, G Law, PJ Tuupanen, S Gylfe, AE Hänninen, UA Cajuso, T Kondelin, J Sarin, AP Pukkala, E Jousilahti, P Salomaa, V Ripatti, S Palotie, A Järvinen, H Renkonen-Sinisalo, L Lepistö, A Böhm, J Mecklin, JP Al-Tassan, NA Palles, C Martin, L Barclay, E Tenesa, A Farrington, SM Timofeeva, MN Meyer, BF Wakil, SM Campbell, H Smith, CG Idziaszczyk, S Maughan, TS Kaplan, R Kerr, R Kerr, D Buchanan, DD Win, AK Hopper, J Jenkins, MA Newcomb, PA Gallinger, S Conti, D Schumacher, FR Casey, G Cheadle, JP Dunlop, MG Tomlinson, IP Houlston, RS Palin, K Aaltonen, LA Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci |
| title | Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci |
| title_full | Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci |
| title_fullStr | Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci |
| title_full_unstemmed | Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci |
| title_short | Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci |
| title_sort | genome wide association study and meta analysis in northern european populations replicate multiple colorectal cancer risk loci |
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