The allelic landscape of human blood cell trait variation and links to common complex disease
Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell,...
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| Format: | Journal article |
| Language: | English |
| Published: |
Cell Press
2016
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| _version_ | 1826259921152245760 |
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| author | Astle, WJ Elding, H Jiang, T Allen, D Ruklisa, D Mann, AL Mead, D Bouman, H Riveros-Mckay, F Kostadima, MA Lambourne, JJ Sivapalaratnam, S Downes, K Kundu, K Bomba, L Berentsen, K Bradley, JR Daugherty, LC Delaneau, O Freson, K Garner, SF Grassi, L Guerrero, J Haimel, M Janssen-Megens, EM Kaan, A Kamat, M Kim, B Mandoli, A Marchini, J Martens, JH Meacham, S Megy, K O'Connell, J Petersen, R Sharifi, N Sheard, SM Staley, JR Tuna, S van der Ent, M Walter, K Wang, SY Wheeler, E Wilder, SP Iotchkova, V Moore, C Sambrook, J Stunnenberg, HG Di Angelantonio, E Kaptoge, S Kuijpers, TW Carrillo-de-Santa-Pau, E Juan, D Rico, D Valencia, A Chen, L Ge, B Vasquez, L Kwan, T Garrido-Martín, D Watt, S Yang, Y Guigo, R Beck, S Paul, DS Pastinen, T Bujold, D Bourque, G Frontini, M Danesh, J Roberts, DJ Ouwehand, WH Butterworth, AS Soranzo, N |
| author_facet | Astle, WJ Elding, H Jiang, T Allen, D Ruklisa, D Mann, AL Mead, D Bouman, H Riveros-Mckay, F Kostadima, MA Lambourne, JJ Sivapalaratnam, S Downes, K Kundu, K Bomba, L Berentsen, K Bradley, JR Daugherty, LC Delaneau, O Freson, K Garner, SF Grassi, L Guerrero, J Haimel, M Janssen-Megens, EM Kaan, A Kamat, M Kim, B Mandoli, A Marchini, J Martens, JH Meacham, S Megy, K O'Connell, J Petersen, R Sharifi, N Sheard, SM Staley, JR Tuna, S van der Ent, M Walter, K Wang, SY Wheeler, E Wilder, SP Iotchkova, V Moore, C Sambrook, J Stunnenberg, HG Di Angelantonio, E Kaptoge, S Kuijpers, TW Carrillo-de-Santa-Pau, E Juan, D Rico, D Valencia, A Chen, L Ge, B Vasquez, L Kwan, T Garrido-Martín, D Watt, S Yang, Y Guigo, R Beck, S Paul, DS Pastinen, T Bujold, D Bourque, G Frontini, M Danesh, J Roberts, DJ Ouwehand, WH Butterworth, AS Soranzo, N |
| author_sort | Astle, WJ |
| collection | OXFORD |
| description | Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we provide evidence of shared genetic pathways linking blood cell indices with complex pathologies, including autoimmune diseases, schizophrenia, and coronary heart disease and evidence suggesting previously reported population associations between blood cell indices and cardiovascular disease may be non-causal. |
| first_indexed | 2024-03-06T18:57:28Z |
| format | Journal article |
| id | oxford-uuid:1255007c-8fab-4730-8662-79c7e574a9c4 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:57:28Z |
| publishDate | 2016 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:1255007c-8fab-4730-8662-79c7e574a9c42022-03-26T10:07:32ZThe allelic landscape of human blood cell trait variation and links to common complex diseaseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1255007c-8fab-4730-8662-79c7e574a9c4EnglishSymplectic Elements at OxfordCell Press2016Astle, WJElding, HJiang, TAllen, DRuklisa, DMann, ALMead, DBouman, HRiveros-Mckay, FKostadima, MALambourne, JJSivapalaratnam, SDownes, KKundu, KBomba, LBerentsen, KBradley, JRDaugherty, LCDelaneau, OFreson, KGarner, SFGrassi, LGuerrero, JHaimel, MJanssen-Megens, EMKaan, AKamat, MKim, BMandoli, AMarchini, JMartens, JHMeacham, SMegy, KO'Connell, JPetersen, RSharifi, NSheard, SMStaley, JRTuna, Svan der Ent, MWalter, KWang, SYWheeler, EWilder, SPIotchkova, VMoore, CSambrook, JStunnenberg, HGDi Angelantonio, EKaptoge, SKuijpers, TWCarrillo-de-Santa-Pau, EJuan, DRico, DValencia, AChen, LGe, BVasquez, LKwan, TGarrido-Martín, DWatt, SYang, YGuigo, RBeck, SPaul, DSPastinen, TBujold, DBourque, GFrontini, MDanesh, JRoberts, DJOuwehand, WHButterworth, ASSoranzo, NMany common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we provide evidence of shared genetic pathways linking blood cell indices with complex pathologies, including autoimmune diseases, schizophrenia, and coronary heart disease and evidence suggesting previously reported population associations between blood cell indices and cardiovascular disease may be non-causal. |
| spellingShingle | Astle, WJ Elding, H Jiang, T Allen, D Ruklisa, D Mann, AL Mead, D Bouman, H Riveros-Mckay, F Kostadima, MA Lambourne, JJ Sivapalaratnam, S Downes, K Kundu, K Bomba, L Berentsen, K Bradley, JR Daugherty, LC Delaneau, O Freson, K Garner, SF Grassi, L Guerrero, J Haimel, M Janssen-Megens, EM Kaan, A Kamat, M Kim, B Mandoli, A Marchini, J Martens, JH Meacham, S Megy, K O'Connell, J Petersen, R Sharifi, N Sheard, SM Staley, JR Tuna, S van der Ent, M Walter, K Wang, SY Wheeler, E Wilder, SP Iotchkova, V Moore, C Sambrook, J Stunnenberg, HG Di Angelantonio, E Kaptoge, S Kuijpers, TW Carrillo-de-Santa-Pau, E Juan, D Rico, D Valencia, A Chen, L Ge, B Vasquez, L Kwan, T Garrido-Martín, D Watt, S Yang, Y Guigo, R Beck, S Paul, DS Pastinen, T Bujold, D Bourque, G Frontini, M Danesh, J Roberts, DJ Ouwehand, WH Butterworth, AS Soranzo, N The allelic landscape of human blood cell trait variation and links to common complex disease |
| title | The allelic landscape of human blood cell trait variation and links to common complex disease |
| title_full | The allelic landscape of human blood cell trait variation and links to common complex disease |
| title_fullStr | The allelic landscape of human blood cell trait variation and links to common complex disease |
| title_full_unstemmed | The allelic landscape of human blood cell trait variation and links to common complex disease |
| title_short | The allelic landscape of human blood cell trait variation and links to common complex disease |
| title_sort | allelic landscape of human blood cell trait variation and links to common complex disease |
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