Meta-analysis and imputation refines the association of 15q25 with smoking quantity
Jonathan Marchini and colleagues with the Ox-GSK consortium report a meta-analysis for smoking phenotypes from 20 studies including 41,150 individuals, confirming an association at the CHRNA5 – CHRNA3 locus on 15q25 to smoking quantity. They use imputation based on 1,000 Genomes Project Pilot 1 data...
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| Veröffentlicht in: | Nature genetics 2010-05, Vol.42 (5), p.436-440 |
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| creator | Liu, Jason Z Tozzi, Federica Waterworth, Dawn M Pillai, Sreekumar G Middleton, Lefkos Berrettini, Wade Knouff, Christopher W Yuan, Xin Waeber, Gérard Vollenweider, Peter Preisig, Martin Wareham, Nicholas J Zhao, Jing Hua Loos, Ruth J F Barroso, Inês Khaw, Kay-Tee Grundy, Scott Barter, Philip Mahley, Robert Kesaniemi, Antero McPherson, Ruth Vincent, John B Strauss, John Kennedy, James L Farmer, Anne McGuffin, Peter Day, Richard Matthews, Keith Bakke, Per Gulsvik, Amund Lucae, Susanne Ising, Marcus Brueckl, Tanja Horstmann, Sonja Wichmann, H-Erich Dahmen, Norbert Lamina, Claudia Polasek, Ozren Zgaga, Lina Campbell, Susan Kooner, Jaspal Chambers, John C Burnett, Mary Susan Devaney, Joseph M Pichard, Augusto D Kent, Kenneth M Satler, Lowell Lindsay, Joseph M Waksman, Ron Epstein, Stephen Wilson, James F Wild, Sarah H Campbell, Harry Vitart, Veronique Reilly, Muredach P Li, Mingyao Qu, Liming Wilensky, Robert Matthai, William Hakonarson, Hakon H Rader, Daniel J Franke, Andre Wittig, Michael Schäfer, Arne Uda, Manuela Terracciano, Antonio Busonero, Fabio Scheet, Paul Schlessinger, David Clair, David St Rujescu, Dan Abecasis, Gonçalo R Grabe, Hans Jörgen Völzke, Henry Petersmann, Astrid John, Ulrich Rudan, Igor Hayward, Caroline Wright, Alan F Kolcic, Ivana Wright, Benjamin J Balmforth, Anthony J Hall, Alistair S Samani, Nilesh J Anderson, Carl A Ahmad, Tariq Mathew, Christopher G Parkes, Miles Satsangi, Jack Caulfield, Mark Munroe, Patricia B Farrall, Martin Dominiczak, Anna Worthington, Jane Thomson, Wendy Eyre, Steve Barton, Anne Mooser, Vincent Francks, Clyde Marchini, Jonathan |
| description | Jonathan Marchini and colleagues with the Ox-GSK consortium report a meta-analysis for smoking phenotypes from 20 studies including 41,150 individuals, confirming an association at the
CHRNA5
–
CHRNA3
locus on 15q25 to smoking quantity. They use imputation based on 1,000 Genomes Project Pilot 1 data to refine the association at this locus.
Smoking is a leading global cause of disease and mortality
1
. We established the Oxford-GlaxoSmithKline study (Ox-GSK) to perform a genome-wide meta-analysis of SNP association with smoking-related behavioral traits. Our final data set included 41,150 individuals drawn from 20 disease, population and control cohorts. Our analysis confirmed an effect on smoking quantity at a locus on 15q25 (
P
= 9.45 × 10
−19
) that includes
CHRNA5
,
CHRNA3
and
CHRNB4
, three genes encoding neuronal nicotinic acetylcholine receptor subunits. We used data from the 1000 Genomes project to investigate the region using imputation, which allowed for analysis of virtually all common SNPs in the region and offered a fivefold increase in marker density over HapMap2 (ref.
2
) as an imputation reference panel. Our fine-mapping approach identified a SNP showing the highest significance, rs55853698, located within the promoter region of
CHRNA5
. Conditional analysis also identified a secondary locus (rs6495308) in
CHRNA3
. |
| doi_str_mv | 10.1038/ng.572 |
| format | Article |
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Tozzi, Federica ; Waterworth, Dawn M ; Pillai, Sreekumar G ; Middleton, Lefkos ; Berrettini, Wade ; Knouff, Christopher W ; Yuan, Xin ; Waeber, Gérard ; Vollenweider, Peter ; Preisig, Martin ; Wareham, Nicholas J ; Zhao, Jing Hua ; Loos, Ruth J F ; Barroso, Inês ; Khaw, Kay-Tee ; Grundy, Scott ; Barter, Philip ; Mahley, Robert ; Kesaniemi, Antero ; McPherson, Ruth ; Vincent, John B ; Strauss, John ; Kennedy, James L ; Farmer, Anne ; McGuffin, Peter ; Day, Richard ; Matthews, Keith ; Bakke, Per ; Gulsvik, Amund ; Lucae, Susanne ; Ising, Marcus ; Brueckl, Tanja ; Horstmann, Sonja ; Wichmann, H-Erich ; Dahmen, Norbert ; Lamina, Claudia ; Polasek, Ozren ; Zgaga, Lina ; Campbell, Susan ; Kooner, Jaspal ; Chambers, John C ; Burnett, Mary Susan ; Devaney, Joseph M ; Pichard, Augusto D ; Kent, Kenneth M ; Satler, Lowell ; Lindsay, Joseph M ; Waksman, Ron ; Epstein, Stephen ; Wilson, James F ; Wild, Sarah H ; Campbell, Harry ; Vitart, Veronique ; Reilly, Muredach P ; Li, Mingyao ; Qu, Liming ; Wilensky, Robert ; Matthai, William ; Hakonarson, Hakon H ; Rader, Daniel J ; Franke, Andre ; Wittig, Michael ; Schäfer, Arne ; Uda, Manuela ; Terracciano, Antonio ; Busonero, Fabio ; Scheet, Paul ; Schlessinger, David ; Clair, David St ; Rujescu, Dan ; Abecasis, Gonçalo R ; Grabe, Hans Jörgen ; Völzke, Henry ; Petersmann, Astrid ; John, Ulrich ; Rudan, Igor ; Hayward, Caroline ; Wright, Alan F ; Kolcic, Ivana ; Wright, Benjamin J ; Balmforth, Anthony J ; Hall, Alistair S ; Samani, Nilesh J ; Anderson, Carl A ; Ahmad, Tariq ; Mathew, Christopher G ; Parkes, Miles ; Satsangi, Jack ; Caulfield, Mark ; Munroe, Patricia B ; Farrall, Martin ; Dominiczak, Anna ; Worthington, Jane ; Thomson, Wendy ; Eyre, Steve ; Barton, Anne ; Mooser, Vincent ; Francks, Clyde ; Marchini, Jonathan</creator><creatorcontrib>Liu, Jason Z ; Tozzi, Federica ; Waterworth, Dawn M ; Pillai, Sreekumar G ; Middleton, Lefkos ; Berrettini, Wade ; Knouff, Christopher W ; Yuan, Xin ; Waeber, Gérard ; Vollenweider, Peter ; Preisig, Martin ; Wareham, Nicholas J ; Zhao, Jing Hua ; Loos, Ruth J F ; Barroso, Inês ; Khaw, Kay-Tee ; Grundy, Scott ; Barter, Philip ; Mahley, Robert ; Kesaniemi, Antero ; McPherson, Ruth ; Vincent, John B ; Strauss, John ; Kennedy, James L ; Farmer, Anne ; McGuffin, Peter ; Day, Richard ; Matthews, Keith ; Bakke, Per ; Gulsvik, Amund ; Lucae, Susanne ; Ising, Marcus ; Brueckl, Tanja ; Horstmann, Sonja ; Wichmann, H-Erich ; Dahmen, Norbert ; Lamina, Claudia ; Polasek, Ozren ; Zgaga, Lina ; Campbell, Susan ; Kooner, Jaspal ; Chambers, John C ; Burnett, Mary Susan ; Devaney, Joseph M ; Pichard, Augusto D ; Kent, Kenneth M ; Satler, Lowell ; Lindsay, Joseph M ; Waksman, Ron ; Epstein, Stephen ; Wilson, James F ; Wild, Sarah H ; Campbell, Harry ; Vitart, Veronique ; Reilly, Muredach P ; Li, Mingyao ; Qu, Liming ; Wilensky, Robert ; Matthai, William ; Hakonarson, Hakon H ; Rader, Daniel J ; Franke, Andre ; Wittig, Michael ; Schäfer, Arne ; Uda, Manuela ; Terracciano, Antonio ; Busonero, Fabio ; Scheet, Paul ; Schlessinger, David ; Clair, David St ; Rujescu, Dan ; Abecasis, Gonçalo R ; Grabe, Hans Jörgen ; Völzke, Henry ; Petersmann, Astrid ; John, Ulrich ; Rudan, Igor ; Hayward, Caroline ; Wright, Alan F ; Kolcic, Ivana ; Wright, Benjamin J ; Balmforth, Anthony J ; Hall, Alistair S ; Samani, Nilesh J ; Anderson, Carl A ; Ahmad, Tariq ; Mathew, Christopher G ; Parkes, Miles ; Satsangi, Jack ; Caulfield, Mark ; Munroe, Patricia B ; Farrall, Martin ; Dominiczak, Anna ; Worthington, Jane ; Thomson, Wendy ; Eyre, Steve ; Barton, Anne ; Mooser, Vincent ; Francks, Clyde ; Marchini, Jonathan ; Wellcome Trust Case Control Consortium ; The Wellcome Trust Case Control Consortium</creatorcontrib><description>Jonathan Marchini and colleagues with the Ox-GSK consortium report a meta-analysis for smoking phenotypes from 20 studies including 41,150 individuals, confirming an association at the
CHRNA5
–
CHRNA3
locus on 15q25 to smoking quantity. They use imputation based on 1,000 Genomes Project Pilot 1 data to refine the association at this locus.
Smoking is a leading global cause of disease and mortality
1
. We established the Oxford-GlaxoSmithKline study (Ox-GSK) to perform a genome-wide meta-analysis of SNP association with smoking-related behavioral traits. Our final data set included 41,150 individuals drawn from 20 disease, population and control cohorts. Our analysis confirmed an effect on smoking quantity at a locus on 15q25 (
P
= 9.45 × 10
−19
) that includes
CHRNA5
,
CHRNA3
and
CHRNB4
, three genes encoding neuronal nicotinic acetylcholine receptor subunits. We used data from the 1000 Genomes project to investigate the region using imputation, which allowed for analysis of virtually all common SNPs in the region and offered a fivefold increase in marker density over HapMap2 (ref.
2
) as an imputation reference panel. Our fine-mapping approach identified a SNP showing the highest significance, rs55853698, located within the promoter region of
CHRNA5
. Conditional analysis also identified a secondary locus (rs6495308) in
CHRNA3
.</description><identifier>ISSN: 1061-4036</identifier><identifier>EISSN: 1546-1718</identifier><identifier>DOI: 10.1038/ng.572</identifier><identifier>PMID: 20418889</identifier><identifier>CODEN: NGENEC</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/208/205/2138 ; 631/208/729/743 ; 692/699/476/5 ; Adult ; Aged ; Agriculture ; Alleles ; Animal Genetics and Genomics ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Chromosome Mapping - methods ; Chromosomes ; Chromosomes, Human, Pair 15 ; Cohort Studies ; Confidence intervals ; Female ; Fundamental and applied biological sciences. Psychology ; Gene Function ; Genetic aspects ; Genetic Markers - genetics ; Genetic susceptibility ; Genetics of eukaryotes. Biological and molecular evolution ; Genome, Human ; Human Genetics ; Humans ; letter ; Male ; Medical sciences ; Meta-analysis ; Middle Aged ; Models, Genetic ; Neurons - metabolism ; Neurosciences ; Nicotine ; Polymorphism, Single Nucleotide ; Receptors, Nicotinic - metabolism ; Risk factors ; Single nucleotide polymorphisms ; Smoking ; Software ; Tobacco habit ; Tobacco, tobacco smoking ; Toxicology</subject><ispartof>Nature genetics, 2010-05, Vol.42 (5), p.436-440</ispartof><rights>Springer Nature America, Inc. 2010</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2010 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group May 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c621t-591797ff9d70a1d72e09f4c1ae2a64189d576317c33b7e53261b89804c6c216b3</citedby><cites>FETCH-LOGICAL-c621t-591797ff9d70a1d72e09f4c1ae2a64189d576317c33b7e53261b89804c6c216b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ng.572$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/ng.572$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23092431$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20418889$$D View this record in 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J</creatorcontrib><creatorcontrib>Balmforth, Anthony J</creatorcontrib><creatorcontrib>Hall, Alistair S</creatorcontrib><creatorcontrib>Samani, Nilesh J</creatorcontrib><creatorcontrib>Anderson, Carl A</creatorcontrib><creatorcontrib>Ahmad, Tariq</creatorcontrib><creatorcontrib>Mathew, Christopher G</creatorcontrib><creatorcontrib>Parkes, Miles</creatorcontrib><creatorcontrib>Satsangi, Jack</creatorcontrib><creatorcontrib>Caulfield, Mark</creatorcontrib><creatorcontrib>Munroe, Patricia B</creatorcontrib><creatorcontrib>Farrall, Martin</creatorcontrib><creatorcontrib>Dominiczak, Anna</creatorcontrib><creatorcontrib>Worthington, Jane</creatorcontrib><creatorcontrib>Thomson, Wendy</creatorcontrib><creatorcontrib>Eyre, Steve</creatorcontrib><creatorcontrib>Barton, Anne</creatorcontrib><creatorcontrib>Mooser, Vincent</creatorcontrib><creatorcontrib>Francks, Clyde</creatorcontrib><creatorcontrib>Marchini, Jonathan</creatorcontrib><creatorcontrib>Wellcome Trust Case Control Consortium</creatorcontrib><creatorcontrib>The Wellcome Trust Case Control Consortium</creatorcontrib><title>Meta-analysis and imputation refines the association of 15q25 with smoking quantity</title><title>Nature genetics</title><addtitle>Nat Genet</addtitle><addtitle>Nat Genet</addtitle><description>Jonathan Marchini and colleagues with the Ox-GSK consortium report a meta-analysis for smoking phenotypes from 20 studies including 41,150 individuals, confirming an association at the
CHRNA5
–
CHRNA3
locus on 15q25 to smoking quantity. They use imputation based on 1,000 Genomes Project Pilot 1 data to refine the association at this locus.
Smoking is a leading global cause of disease and mortality
1
. We established the Oxford-GlaxoSmithKline study (Ox-GSK) to perform a genome-wide meta-analysis of SNP association with smoking-related behavioral traits. Our final data set included 41,150 individuals drawn from 20 disease, population and control cohorts. Our analysis confirmed an effect on smoking quantity at a locus on 15q25 (
P
= 9.45 × 10
−19
) that includes
CHRNA5
,
CHRNA3
and
CHRNB4
, three genes encoding neuronal nicotinic acetylcholine receptor subunits. We used data from the 1000 Genomes project to investigate the region using imputation, which allowed for analysis of virtually all common SNPs in the region and offered a fivefold increase in marker density over HapMap2 (ref.
2
) as an imputation reference panel. Our fine-mapping approach identified a SNP showing the highest significance, rs55853698, located within the promoter region of
CHRNA5
. Conditional analysis also identified a secondary locus (rs6495308) in
CHRNA3
.</description><subject>631/208/205/2138</subject><subject>631/208/729/743</subject><subject>692/699/476/5</subject><subject>Adult</subject><subject>Aged</subject><subject>Agriculture</subject><subject>Alleles</subject><subject>Animal Genetics and Genomics</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Chromosome Mapping - methods</subject><subject>Chromosomes</subject><subject>Chromosomes, Human, Pair 15</subject><subject>Cohort Studies</subject><subject>Confidence intervals</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Function</subject><subject>Genetic aspects</subject><subject>Genetic Markers - genetics</subject><subject>Genetic susceptibility</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Genome, Human</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>letter</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Meta-analysis</subject><subject>Middle Aged</subject><subject>Models, Genetic</subject><subject>Neurons - metabolism</subject><subject>Neurosciences</subject><subject>Nicotine</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Receptors, Nicotinic - metabolism</subject><subject>Risk factors</subject><subject>Single nucleotide polymorphisms</subject><subject>Smoking</subject><subject>Software</subject><subject>Tobacco habit</subject><subject>Tobacco, tobacco 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and imputation refines the association of 15q25 with smoking quantity</title><author>Liu, Jason Z ; Tozzi, Federica ; Waterworth, Dawn M ; Pillai, Sreekumar G ; Middleton, Lefkos ; Berrettini, Wade ; Knouff, Christopher W ; Yuan, Xin ; Waeber, Gérard ; Vollenweider, Peter ; Preisig, Martin ; Wareham, Nicholas J ; Zhao, Jing Hua ; Loos, Ruth J F ; Barroso, Inês ; Khaw, Kay-Tee ; Grundy, Scott ; Barter, Philip ; Mahley, Robert ; Kesaniemi, Antero ; McPherson, Ruth ; Vincent, John B ; Strauss, John ; Kennedy, James L ; Farmer, Anne ; McGuffin, Peter ; Day, Richard ; Matthews, Keith ; Bakke, Per ; Gulsvik, Amund ; Lucae, Susanne ; Ising, Marcus ; Brueckl, Tanja ; Horstmann, Sonja ; Wichmann, H-Erich ; Dahmen, Norbert ; Lamina, Claudia ; Polasek, Ozren ; Zgaga, Lina ; Campbell, Susan ; Kooner, Jaspal ; Chambers, John C ; Burnett, Mary Susan ; Devaney, Joseph M ; Pichard, Augusto D ; Kent, Kenneth M ; Satler, Lowell ; Lindsay, Joseph M ; Waksman, Ron ; Epstein, Stephen ; Wilson, James F ; Wild, Sarah H ; Campbell, Harry ; Vitart, Veronique ; Reilly, Muredach P ; Li, Mingyao ; Qu, Liming ; Wilensky, Robert ; Matthai, William ; Hakonarson, Hakon H ; Rader, Daniel J ; Franke, Andre ; Wittig, Michael ; Schäfer, Arne ; Uda, Manuela ; Terracciano, Antonio ; Busonero, Fabio ; Scheet, Paul ; Schlessinger, David ; Clair, David St ; Rujescu, Dan ; Abecasis, Gonçalo R ; Grabe, Hans Jörgen ; Völzke, Henry ; Petersmann, Astrid ; John, Ulrich ; Rudan, Igor ; Hayward, Caroline ; Wright, Alan F ; Kolcic, Ivana ; Wright, Benjamin J ; Balmforth, Anthony J ; Hall, Alistair S ; Samani, Nilesh J ; Anderson, Carl A ; Ahmad, Tariq ; Mathew, Christopher G ; Parkes, Miles ; Satsangi, Jack ; Caulfield, Mark ; Munroe, Patricia B ; Farrall, Martin ; Dominiczak, Anna ; Worthington, Jane ; Thomson, Wendy ; Eyre, Steve ; Barton, Anne ; Mooser, Vincent ; Francks, Clyde ; Marchini, 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Psychology</topic><topic>Gene Function</topic><topic>Genetic aspects</topic><topic>Genetic Markers - genetics</topic><topic>Genetic susceptibility</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Genome, Human</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>letter</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Meta-analysis</topic><topic>Middle Aged</topic><topic>Models, Genetic</topic><topic>Neurons - metabolism</topic><topic>Neurosciences</topic><topic>Nicotine</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Receptors, Nicotinic - metabolism</topic><topic>Risk factors</topic><topic>Single nucleotide polymorphisms</topic><topic>Smoking</topic><topic>Software</topic><topic>Tobacco habit</topic><topic>Tobacco, tobacco smoking</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Jason Z</creatorcontrib><creatorcontrib>Tozzi, Federica</creatorcontrib><creatorcontrib>Waterworth, Dawn M</creatorcontrib><creatorcontrib>Pillai, Sreekumar G</creatorcontrib><creatorcontrib>Middleton, 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Robert</au><au>Kesaniemi, Antero</au><au>McPherson, Ruth</au><au>Vincent, John B</au><au>Strauss, John</au><au>Kennedy, James L</au><au>Farmer, Anne</au><au>McGuffin, Peter</au><au>Day, Richard</au><au>Matthews, Keith</au><au>Bakke, Per</au><au>Gulsvik, Amund</au><au>Lucae, Susanne</au><au>Ising, Marcus</au><au>Brueckl, Tanja</au><au>Horstmann, Sonja</au><au>Wichmann, H-Erich</au><au>Dahmen, Norbert</au><au>Lamina, Claudia</au><au>Polasek, Ozren</au><au>Zgaga, Lina</au><au>Campbell, Susan</au><au>Kooner, Jaspal</au><au>Chambers, John C</au><au>Burnett, Mary Susan</au><au>Devaney, Joseph M</au><au>Pichard, Augusto D</au><au>Kent, Kenneth M</au><au>Satler, Lowell</au><au>Lindsay, Joseph M</au><au>Waksman, Ron</au><au>Epstein, Stephen</au><au>Wilson, James F</au><au>Wild, Sarah H</au><au>Campbell, Harry</au><au>Vitart, Veronique</au><au>Reilly, Muredach P</au><au>Li, Mingyao</au><au>Qu, Liming</au><au>Wilensky, Robert</au><au>Matthai, William</au><au>Hakonarson, Hakon H</au><au>Rader, Daniel J</au><au>Franke, Andre</au><au>Wittig, Michael</au><au>Schäfer, Arne</au><au>Uda, Manuela</au><au>Terracciano, Antonio</au><au>Busonero, Fabio</au><au>Scheet, Paul</au><au>Schlessinger, David</au><au>Clair, David St</au><au>Rujescu, Dan</au><au>Abecasis, Gonçalo R</au><au>Grabe, Hans Jörgen</au><au>Völzke, Henry</au><au>Petersmann, Astrid</au><au>John, Ulrich</au><au>Rudan, Igor</au><au>Hayward, Caroline</au><au>Wright, Alan F</au><au>Kolcic, Ivana</au><au>Wright, Benjamin J</au><au>Balmforth, Anthony J</au><au>Hall, Alistair S</au><au>Samani, Nilesh J</au><au>Anderson, Carl A</au><au>Ahmad, Tariq</au><au>Mathew, Christopher G</au><au>Parkes, Miles</au><au>Satsangi, Jack</au><au>Caulfield, Mark</au><au>Munroe, Patricia B</au><au>Farrall, Martin</au><au>Dominiczak, Anna</au><au>Worthington, Jane</au><au>Thomson, Wendy</au><au>Eyre, Steve</au><au>Barton, Anne</au><au>Mooser, Vincent</au><au>Francks, Clyde</au><au>Marchini, Jonathan</au><aucorp>Wellcome Trust Case Control Consortium</aucorp><aucorp>The Wellcome Trust Case Control Consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Meta-analysis and imputation refines the association of 15q25 with smoking quantity</atitle><jtitle>Nature genetics</jtitle><stitle>Nat Genet</stitle><addtitle>Nat Genet</addtitle><date>2010-05-01</date><risdate>2010</risdate><volume>42</volume><issue>5</issue><spage>436</spage><epage>440</epage><pages>436-440</pages><issn>1061-4036</issn><eissn>1546-1718</eissn><coden>NGENEC</coden><abstract>Jonathan Marchini and colleagues with the Ox-GSK consortium report a meta-analysis for smoking phenotypes from 20 studies including 41,150 individuals, confirming an association at the
CHRNA5
–
CHRNA3
locus on 15q25 to smoking quantity. They use imputation based on 1,000 Genomes Project Pilot 1 data to refine the association at this locus.
Smoking is a leading global cause of disease and mortality
1
. We established the Oxford-GlaxoSmithKline study (Ox-GSK) to perform a genome-wide meta-analysis of SNP association with smoking-related behavioral traits. Our final data set included 41,150 individuals drawn from 20 disease, population and control cohorts. Our analysis confirmed an effect on smoking quantity at a locus on 15q25 (
P
= 9.45 × 10
−19
) that includes
CHRNA5
,
CHRNA3
and
CHRNB4
, three genes encoding neuronal nicotinic acetylcholine receptor subunits. We used data from the 1000 Genomes project to investigate the region using imputation, which allowed for analysis of virtually all common SNPs in the region and offered a fivefold increase in marker density over HapMap2 (ref.
2
) as an imputation reference panel. Our fine-mapping approach identified a SNP showing the highest significance, rs55853698, located within the promoter region of
CHRNA5
. Conditional analysis also identified a secondary locus (rs6495308) in
CHRNA3
.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>20418889</pmid><doi>10.1038/ng.572</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1061-4036 |
| ispartof | Nature genetics, 2010-05, Vol.42 (5), p.436-440 |
| issn | 1061-4036 1546-1718 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3612983 |
| source | MEDLINE; Nature Journals Online; SpringerLink Journals - AutoHoldings |
| subjects | 631/208/205/2138 631/208/729/743 692/699/476/5 Adult Aged Agriculture Alleles Animal Genetics and Genomics Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Research Chromosome Mapping - methods Chromosomes Chromosomes, Human, Pair 15 Cohort Studies Confidence intervals Female Fundamental and applied biological sciences. Psychology Gene Function Genetic aspects Genetic Markers - genetics Genetic susceptibility Genetics of eukaryotes. Biological and molecular evolution Genome, Human Human Genetics Humans letter Male Medical sciences Meta-analysis Middle Aged Models, Genetic Neurons - metabolism Neurosciences Nicotine Polymorphism, Single Nucleotide Receptors, Nicotinic - metabolism Risk factors Single nucleotide polymorphisms Smoking Software Tobacco habit Tobacco, tobacco smoking Toxicology |
| title | Meta-analysis and imputation refines the association of 15q25 with smoking quantity |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T12%3A32%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Meta-analysis%20and%20imputation%20refines%20the%20association%20of%2015q25%20with%20smoking%20quantity&rft.jtitle=Nature%20genetics&rft.au=Liu,%20Jason%20Z&rft.aucorp=Wellcome%20Trust%20Case%20Control%20Consortium&rft.date=2010-05-01&rft.volume=42&rft.issue=5&rft.spage=436&rft.epage=440&rft.pages=436-440&rft.issn=1061-4036&rft.eissn=1546-1718&rft.coden=NGENEC&rft_id=info:doi/10.1038/ng.572&rft_dat=%3Cgale_pubme%3EA225741123%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=222682801&rft_id=info:pmid/20418889&rft_galeid=A225741123&rfr_iscdi=true |