Fetal hemoglobin in sickle cell anemia: genome-wide association studies suggest a regulatory region in the 5′ olfactory receptor gene cluster
In a genome-wide association study of 848 blacks with sickle cell anemia, we identified single nucleotide polymorphisms (SNPs) associated with fetal hemoglobin concentration. The most significant SNPs in a discovery sample were tested in a replication set of 305 blacks with sickle cell anemia and in...
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| Veröffentlicht in: | Blood 2010-03, Vol.115 (9), p.1815-1822 |
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| creator | Solovieff, Nadia Milton, Jacqueline N. Hartley, Stephen W. Sherva, Richard Sebastiani, Paola Dworkis, Daniel A. Klings, Elizabeth S. Farrer, Lindsay A. Garrett, Melanie E. Ashley-Koch, Allison Telen, Marilyn J. Fucharoen, Supan Ha, Shau Yin Li, Chi-Kong Chui, David H.K. Baldwin, Clinton T. Steinberg, Martin H. |
| description | In a genome-wide association study of 848 blacks with sickle cell anemia, we identified single nucleotide polymorphisms (SNPs) associated with fetal hemoglobin concentration. The most significant SNPs in a discovery sample were tested in a replication set of 305 blacks with sickle cell anemia and in subjects with hemoglobin E or β thalassemia trait from Thailand and Hong Kong. A novel region on chromosome 11 containing olfactory receptor genes OR51B5 and OR51B6 was identified by 6 SNPs (lowest P = 4.7E−08) and validated in the replication set. An additional olfactory receptor gene, OR51B2, was identified by a novel SNP set enrichment analysis. Genome-wide association studies also validated a previously identified SNP (rs766432) in BCL11A, a gene known to affect fetal hemoglobin levels (P = 2.6E−21) and in Thailand and Hong Kong subjects. Elements within the olfactory receptor gene cluster might play a regulatory role in γ-globin gene expression. |
| doi_str_mv | 10.1182/blood-2009-08-239517 |
| format | Article |
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The most significant SNPs in a discovery sample were tested in a replication set of 305 blacks with sickle cell anemia and in subjects with hemoglobin E or β thalassemia trait from Thailand and Hong Kong. A novel region on chromosome 11 containing olfactory receptor genes OR51B5 and OR51B6 was identified by 6 SNPs (lowest P = 4.7E−08) and validated in the replication set. An additional olfactory receptor gene, OR51B2, was identified by a novel SNP set enrichment analysis. Genome-wide association studies also validated a previously identified SNP (rs766432) in BCL11A, a gene known to affect fetal hemoglobin levels (P = 2.6E−21) and in Thailand and Hong Kong subjects. Elements within the olfactory receptor gene cluster might play a regulatory role in γ-globin gene expression.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2009-08-239517</identifier><identifier>PMID: 20018918</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Anemia, Sickle Cell - blood ; Anemia, Sickle Cell - genetics ; Anemias. Hemoglobinopathies ; beta-Thalassemia - genetics ; Biological and medical sciences ; Black or African American - genetics ; Carrier Proteins - genetics ; Child ; Child, Preschool ; Chromosomes, Human, Pair 11 - genetics ; Chromosomes, Human, X - genetics ; Diseases of red blood cells ; Female ; Fetal Hemoglobin - genetics ; Fetal Hemoglobin - metabolism ; Genome-Wide Association Study ; Hematologic and hematopoietic diseases ; Hemoglobin E - genetics ; Hong Kong ; Humans ; Male ; Medical sciences ; Multigene Family ; Nuclear Proteins - genetics ; Polymorphism, Single Nucleotide ; Receptors, Odorant - genetics ; Red Cells, Iron, and Erythropoiesis ; Regulatory Sequences, Nucleic Acid ; Repressor Proteins ; Thailand ; Young Adult</subject><ispartof>Blood, 2010-03, Vol.115 (9), p.1815-1822</ispartof><rights>2010 American Society of Hematology</rights><rights>2015 INIST-CNRS</rights><rights>2010 by The American Society of Hematology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c492t-33d848db767ea46ad16324bae2f078f6792acde65aec70e322c671cf51b072ed3</citedby><cites>FETCH-LOGICAL-c492t-33d848db767ea46ad16324bae2f078f6792acde65aec70e322c671cf51b072ed3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,777,781,882,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22509967$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20018918$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Solovieff, Nadia</creatorcontrib><creatorcontrib>Milton, Jacqueline N.</creatorcontrib><creatorcontrib>Hartley, Stephen W.</creatorcontrib><creatorcontrib>Sherva, Richard</creatorcontrib><creatorcontrib>Sebastiani, Paola</creatorcontrib><creatorcontrib>Dworkis, Daniel A.</creatorcontrib><creatorcontrib>Klings, Elizabeth S.</creatorcontrib><creatorcontrib>Farrer, Lindsay A.</creatorcontrib><creatorcontrib>Garrett, Melanie E.</creatorcontrib><creatorcontrib>Ashley-Koch, Allison</creatorcontrib><creatorcontrib>Telen, Marilyn J.</creatorcontrib><creatorcontrib>Fucharoen, Supan</creatorcontrib><creatorcontrib>Ha, Shau Yin</creatorcontrib><creatorcontrib>Li, Chi-Kong</creatorcontrib><creatorcontrib>Chui, David H.K.</creatorcontrib><creatorcontrib>Baldwin, Clinton T.</creatorcontrib><creatorcontrib>Steinberg, Martin H.</creatorcontrib><title>Fetal hemoglobin in sickle cell anemia: genome-wide association studies suggest a regulatory region in the 5′ olfactory receptor gene cluster</title><title>Blood</title><addtitle>Blood</addtitle><description>In a genome-wide association study of 848 blacks with sickle cell anemia, we identified single nucleotide polymorphisms (SNPs) associated with fetal hemoglobin concentration. The most significant SNPs in a discovery sample were tested in a replication set of 305 blacks with sickle cell anemia and in subjects with hemoglobin E or β thalassemia trait from Thailand and Hong Kong. A novel region on chromosome 11 containing olfactory receptor genes OR51B5 and OR51B6 was identified by 6 SNPs (lowest P = 4.7E−08) and validated in the replication set. An additional olfactory receptor gene, OR51B2, was identified by a novel SNP set enrichment analysis. Genome-wide association studies also validated a previously identified SNP (rs766432) in BCL11A, a gene known to affect fetal hemoglobin levels (P = 2.6E−21) and in Thailand and Hong Kong subjects. Elements within the olfactory receptor gene cluster might play a regulatory role in γ-globin gene expression.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Anemia, Sickle Cell - blood</subject><subject>Anemia, Sickle Cell - genetics</subject><subject>Anemias. Hemoglobinopathies</subject><subject>beta-Thalassemia - genetics</subject><subject>Biological and medical sciences</subject><subject>Black or African American - genetics</subject><subject>Carrier Proteins - genetics</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Chromosomes, Human, Pair 11 - genetics</subject><subject>Chromosomes, Human, X - genetics</subject><subject>Diseases of red blood cells</subject><subject>Female</subject><subject>Fetal Hemoglobin - genetics</subject><subject>Fetal Hemoglobin - metabolism</subject><subject>Genome-Wide Association Study</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hemoglobin E - genetics</subject><subject>Hong Kong</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Multigene Family</subject><subject>Nuclear Proteins - genetics</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Receptors, Odorant - genetics</subject><subject>Red Cells, Iron, and Erythropoiesis</subject><subject>Regulatory Sequences, Nucleic Acid</subject><subject>Repressor Proteins</subject><subject>Thailand</subject><subject>Young Adult</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kctu1DAUhi0EosPAGyDkDWIV8CWJHRZIVUUBqRIbWFuOfZIxOPFgO0Xd9Q36LjwST4LDDC1skCz5SOc__7l8CD2l5CWlkr3qfQi2YoR0FZEV411DxT20oQ2TFSGM3EcbQkhb1Z2gJ-hRSl8IoTVnzUN0Uqqo7KjcoJtzyNrjHUxh9KF3My4vOfPVAzbgPdYzTE6_xiPMYYLqu7OAdUrBOJ1dKNq8WAcJp2UcIWWscYRx8TqHeLWGq6ZY5h3g5uf1Dxz8oM0xaWBfotW6NPNLyhAfoweD9gmeHP8t-nz-9tPZ--ri47sPZ6cXlak7livOrayl7UUrQNettrTlrO41sIEIObSiY9pYaBsNRhDgjJlWUDM0tCeCgeVb9Obgu1_6CayBOUft1T66SccrFbRT_2Zmt1NjuFRMciZLty16cTSI4dtSNleTS-vFysHCkpTgvBV1oVKU9UFpYkgpwnDbhRK1olS_UaoVpSJSHVCWsmd_T3hb9IddETw_CnQy2g9Rz8alOx1rSNe14m5VKPe8dBBVMg5mA9YVBFnZ4P4_yS8Ko8KO</recordid><startdate>20100304</startdate><enddate>20100304</enddate><creator>Solovieff, Nadia</creator><creator>Milton, Jacqueline N.</creator><creator>Hartley, Stephen W.</creator><creator>Sherva, Richard</creator><creator>Sebastiani, Paola</creator><creator>Dworkis, Daniel A.</creator><creator>Klings, Elizabeth S.</creator><creator>Farrer, Lindsay A.</creator><creator>Garrett, Melanie E.</creator><creator>Ashley-Koch, Allison</creator><creator>Telen, Marilyn J.</creator><creator>Fucharoen, Supan</creator><creator>Ha, Shau Yin</creator><creator>Li, Chi-Kong</creator><creator>Chui, David H.K.</creator><creator>Baldwin, Clinton T.</creator><creator>Steinberg, Martin H.</creator><general>Elsevier Inc</general><general>Americain Society of Hematology</general><general>American Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20100304</creationdate><title>Fetal hemoglobin in sickle cell anemia: genome-wide association studies suggest a regulatory region in the 5′ olfactory receptor gene cluster</title><author>Solovieff, Nadia ; Milton, Jacqueline N. ; Hartley, Stephen W. ; Sherva, Richard ; Sebastiani, Paola ; Dworkis, Daniel A. ; Klings, Elizabeth S. ; Farrer, Lindsay A. ; Garrett, Melanie E. ; Ashley-Koch, Allison ; Telen, Marilyn J. ; Fucharoen, Supan ; Ha, Shau Yin ; Li, Chi-Kong ; Chui, David H.K. ; Baldwin, Clinton T. ; Steinberg, Martin H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c492t-33d848db767ea46ad16324bae2f078f6792acde65aec70e322c671cf51b072ed3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Anemia, Sickle Cell - blood</topic><topic>Anemia, Sickle Cell - genetics</topic><topic>Anemias. Hemoglobinopathies</topic><topic>beta-Thalassemia - genetics</topic><topic>Biological and medical sciences</topic><topic>Black or African American - genetics</topic><topic>Carrier Proteins - genetics</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Chromosomes, Human, Pair 11 - genetics</topic><topic>Chromosomes, Human, X - genetics</topic><topic>Diseases of red blood cells</topic><topic>Female</topic><topic>Fetal Hemoglobin - genetics</topic><topic>Fetal Hemoglobin - metabolism</topic><topic>Genome-Wide Association Study</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hemoglobin E - genetics</topic><topic>Hong Kong</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Multigene Family</topic><topic>Nuclear Proteins - genetics</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Receptors, Odorant - genetics</topic><topic>Red Cells, Iron, and Erythropoiesis</topic><topic>Regulatory Sequences, Nucleic Acid</topic><topic>Repressor Proteins</topic><topic>Thailand</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Solovieff, Nadia</creatorcontrib><creatorcontrib>Milton, Jacqueline N.</creatorcontrib><creatorcontrib>Hartley, Stephen W.</creatorcontrib><creatorcontrib>Sherva, Richard</creatorcontrib><creatorcontrib>Sebastiani, Paola</creatorcontrib><creatorcontrib>Dworkis, Daniel A.</creatorcontrib><creatorcontrib>Klings, Elizabeth S.</creatorcontrib><creatorcontrib>Farrer, Lindsay A.</creatorcontrib><creatorcontrib>Garrett, Melanie E.</creatorcontrib><creatorcontrib>Ashley-Koch, Allison</creatorcontrib><creatorcontrib>Telen, Marilyn J.</creatorcontrib><creatorcontrib>Fucharoen, Supan</creatorcontrib><creatorcontrib>Ha, Shau Yin</creatorcontrib><creatorcontrib>Li, Chi-Kong</creatorcontrib><creatorcontrib>Chui, David H.K.</creatorcontrib><creatorcontrib>Baldwin, Clinton T.</creatorcontrib><creatorcontrib>Steinberg, Martin H.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Solovieff, Nadia</au><au>Milton, Jacqueline N.</au><au>Hartley, Stephen W.</au><au>Sherva, Richard</au><au>Sebastiani, Paola</au><au>Dworkis, Daniel A.</au><au>Klings, Elizabeth S.</au><au>Farrer, Lindsay A.</au><au>Garrett, Melanie E.</au><au>Ashley-Koch, Allison</au><au>Telen, Marilyn J.</au><au>Fucharoen, Supan</au><au>Ha, Shau Yin</au><au>Li, Chi-Kong</au><au>Chui, David H.K.</au><au>Baldwin, Clinton T.</au><au>Steinberg, Martin H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fetal hemoglobin in sickle cell anemia: genome-wide association studies suggest a regulatory region in the 5′ olfactory receptor gene cluster</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2010-03-04</date><risdate>2010</risdate><volume>115</volume><issue>9</issue><spage>1815</spage><epage>1822</epage><pages>1815-1822</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>In a genome-wide association study of 848 blacks with sickle cell anemia, we identified single nucleotide polymorphisms (SNPs) associated with fetal hemoglobin concentration. The most significant SNPs in a discovery sample were tested in a replication set of 305 blacks with sickle cell anemia and in subjects with hemoglobin E or β thalassemia trait from Thailand and Hong Kong. A novel region on chromosome 11 containing olfactory receptor genes OR51B5 and OR51B6 was identified by 6 SNPs (lowest P = 4.7E−08) and validated in the replication set. An additional olfactory receptor gene, OR51B2, was identified by a novel SNP set enrichment analysis. Genome-wide association studies also validated a previously identified SNP (rs766432) in BCL11A, a gene known to affect fetal hemoglobin levels (P = 2.6E−21) and in Thailand and Hong Kong subjects. Elements within the olfactory receptor gene cluster might play a regulatory role in γ-globin gene expression.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>20018918</pmid><doi>10.1182/blood-2009-08-239517</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adolescent Adult Anemia, Sickle Cell - blood Anemia, Sickle Cell - genetics Anemias. Hemoglobinopathies beta-Thalassemia - genetics Biological and medical sciences Black or African American - genetics Carrier Proteins - genetics Child Child, Preschool Chromosomes, Human, Pair 11 - genetics Chromosomes, Human, X - genetics Diseases of red blood cells Female Fetal Hemoglobin - genetics Fetal Hemoglobin - metabolism Genome-Wide Association Study Hematologic and hematopoietic diseases Hemoglobin E - genetics Hong Kong Humans Male Medical sciences Multigene Family Nuclear Proteins - genetics Polymorphism, Single Nucleotide Receptors, Odorant - genetics Red Cells, Iron, and Erythropoiesis Regulatory Sequences, Nucleic Acid Repressor Proteins Thailand Young Adult |
| title | Fetal hemoglobin in sickle cell anemia: genome-wide association studies suggest a regulatory region in the 5′ olfactory receptor gene cluster |
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