Trans-ancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders
Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried...
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| Veröffentlicht in: | Nature neuroscience 2018-11, Vol.21 (12), p.1656-1669 |
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| creator | Walters, Raymond K. Polimanti, Renato Johnson, Emma C. McClintick, Jeanette N. Adams, Mark J. Adkins, Amy E. Aliev, Fazil Bacanu, Silviu-Alin Batzler, Anthony Bertelsen, Sarah Biernacka, Joanna M. Bigdeli, Tim B. Chen, Li-Shiun Clarke, Toni-Kim Chou, Yi-Ling Degenhardt, Franziska Docherty, Anna R. Edwards, Alexis C. Fontanillas, Pierre Foo, Jerome C. Fox, Louis Frank, Josef Giegling, Ina Gordon, Scott Hack, Laura M. Hartmann, Annette M. Hartz, Sarah M. Heilmann-Heimbach, Stefanie Herms, Stefan Hodgkinson, Colin Hoffmann, Per Hottenga, Jouke Jan Kennedy, Martin A. Alanne-Kinnunen, Mervi Konte, Bettina Lahti, Jari Lahti-Pulkkinen, Marius Lai, Dongbing Ligthart, Lannie Loukola, Anu Maher, Brion S. Mbarek, Hamdi McIntosh, Andrew M. McQueen, Matthew B. Meyers, Jacquelyn L. Milaneschi, Yuri Palviainen, Teemu Pearson, John F. Peterson, Roseann E. Ripatti, Samuli Ryu, Euijung Saccone, Nancy L. Salvatore, Jessica E. Sanchez-Roige, Sandra Schwandt, Melanie Sherva, Richard Streit, Fabian Strohmaier, Jana Thomas, Nathaniel Wang, Jen-Chyong Webb, Bradley T. Wedow, Robbee Wetherill, Leah Wills, Amanda G. Boardman, Jason D. Chen, Danfeng Choi, Doo-Sup Copeland, William E. Culverhouse, Robert C. Dahmen, Norbert Degenhardt, Louisa Domingue, Benjamin W. Elson, Sarah L. Frye, Mark A. Gäbel, Wolfgang Hayward, Caroline Ising, Marcus Keyes, Margaret Kiefer, Falk Kramer, John Kuperman, Samuel Lucae, Susanne Lynskey, Michael T. Maier, Wolfgang Mann, Karl Männistö, Satu Müller-Myhsok, Bertram Murray, Alison D. Nurnberger, John I. Palotie, Aarno Preuss, Ulrich Räikkönen, Katri Reynolds, Maureen D. Ridinger, Monika Scherbaum, Norbert Schuckit, Marc A. Soyka, Michael Treutlein, Jens Witt, Stephanie |
| description | Liability to alcohol dependence (AD) is heritable, but little is known
about its complex polygenic architecture or its genetic relationship with other
disorders. To discover loci associated with AD and characterize the relationship
between AD and other psychiatric and behavioral outcomes, we carried out the
largest GWAS to date of DSM-IV diagnosed AD. Genome-wide data on 14,904
individuals with AD and 37,944 controls from 28 case/control and family-based
studies were meta-analyzed, stratified by genetic ancestry (European, N =
46,568; African; N = 6,280). Independent, genome-wide significant effects of
different
ADH1B
variants were identified in European
(rs1229984; p = 9.8E-13) and African ancestries (rs2066702; p = 2.2E-9).
Significant genetic correlations were observed with 17 phenotypes, including
schizophrenia, ADHD, depression, and use of cigarettes and cannabis. The genetic
underpinnings of AD only partially overlap with those for alcohol consumption,
underscoring the genetic distinction between pathological and non-pathological
drinking behaviors. |
| doi_str_mv | 10.1038/s41593-018-0275-1 |
| format | Article |
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about its complex polygenic architecture or its genetic relationship with other
disorders. To discover loci associated with AD and characterize the relationship
between AD and other psychiatric and behavioral outcomes, we carried out the
largest GWAS to date of DSM-IV diagnosed AD. Genome-wide data on 14,904
individuals with AD and 37,944 controls from 28 case/control and family-based
studies were meta-analyzed, stratified by genetic ancestry (European, N =
46,568; African; N = 6,280). Independent, genome-wide significant effects of
different
ADH1B
variants were identified in European
(rs1229984; p = 9.8E-13) and African ancestries (rs2066702; p = 2.2E-9).
Significant genetic correlations were observed with 17 phenotypes, including
schizophrenia, ADHD, depression, and use of cigarettes and cannabis. The genetic
underpinnings of AD only partially overlap with those for alcohol consumption,
underscoring the genetic distinction between pathological and non-pathological
drinking behaviors.</description><identifier>ISSN: 1097-6256</identifier><identifier>EISSN: 1546-1726</identifier><identifier>DOI: 10.1038/s41593-018-0275-1</identifier><identifier>PMID: 30482948</identifier><language>eng</language><ispartof>Nature neuroscience, 2018-11, Vol.21 (12), p.1656-1669</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids></links><search><creatorcontrib>Walters, Raymond K.</creatorcontrib><creatorcontrib>Polimanti, Renato</creatorcontrib><creatorcontrib>Johnson, Emma C.</creatorcontrib><creatorcontrib>McClintick, Jeanette N.</creatorcontrib><creatorcontrib>Adams, Mark J.</creatorcontrib><creatorcontrib>Adkins, Amy E.</creatorcontrib><creatorcontrib>Aliev, 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Bertram</creatorcontrib><creatorcontrib>Murray, Alison D.</creatorcontrib><creatorcontrib>Nurnberger, John I.</creatorcontrib><creatorcontrib>Palotie, Aarno</creatorcontrib><creatorcontrib>Preuss, Ulrich</creatorcontrib><creatorcontrib>Räikkönen, Katri</creatorcontrib><creatorcontrib>Reynolds, Maureen D.</creatorcontrib><creatorcontrib>Ridinger, Monika</creatorcontrib><creatorcontrib>Scherbaum, Norbert</creatorcontrib><creatorcontrib>Schuckit, Marc A.</creatorcontrib><creatorcontrib>Soyka, Michael</creatorcontrib><creatorcontrib>Treutlein, Jens</creatorcontrib><creatorcontrib>Witt, Stephanie</creatorcontrib><title>Trans-ancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders</title><title>Nature neuroscience</title><description>Liability to alcohol dependence (AD) is heritable, but little is known
about its complex polygenic architecture or its genetic relationship with other
disorders. To discover loci associated with AD and characterize the relationship
between AD and other psychiatric and behavioral outcomes, we carried out the
largest GWAS to date of DSM-IV diagnosed AD. Genome-wide data on 14,904
individuals with AD and 37,944 controls from 28 case/control and family-based
studies were meta-analyzed, stratified by genetic ancestry (European, N =
46,568; African; N = 6,280). Independent, genome-wide significant effects of
different
ADH1B
variants were identified in European
(rs1229984; p = 9.8E-13) and African ancestries (rs2066702; p = 2.2E-9).
Significant genetic correlations were observed with 17 phenotypes, including
schizophrenia, ADHD, depression, and use of cigarettes and cannabis. The genetic
underpinnings of AD only partially overlap with those for alcohol consumption,
underscoring the genetic distinction between pathological and non-pathological
drinking behaviors.</description><issn>1097-6256</issn><issn>1546-1726</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNqljs9KxDAYxIMo7vrnAbzlBaJfmiZNL4KIrncXPJaYfttmaZOQdFf27Y3gxbOnGfjNDEPIHYd7DkI_5JrLVjDgmkHVSMbPyJrLWjHeVOq8eGgbpiqpVuQq5z0ANFK3l2QloNZVW-s12W-T8ZkZbzEvyUx08_H0TsOOmsmGMUy0x4i-x8JpwiOaKVMb5jl4OqDHxVl6KDhF573zQ6ZfbhlpzCc7OrOkgnuXQyqJfEMudqWOt796TR5fX7bPbywePmfsLfqfA11Mbjbp1AXjur_Eu7EbwrFTtYAKGvHvgW8-T2kC</recordid><startdate>20181126</startdate><enddate>20181126</enddate><creator>Walters, Raymond K.</creator><creator>Polimanti, Renato</creator><creator>Johnson, Emma C.</creator><creator>McClintick, Jeanette N.</creator><creator>Adams, Mark J.</creator><creator>Adkins, Amy E.</creator><creator>Aliev, Fazil</creator><creator>Bacanu, Silviu-Alin</creator><creator>Batzler, Anthony</creator><creator>Bertelsen, Sarah</creator><creator>Biernacka, Joanna M.</creator><creator>Bigdeli, Tim 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Jari ; Lahti-Pulkkinen, Marius ; Lai, Dongbing ; Ligthart, Lannie ; Loukola, Anu ; Maher, Brion S. ; Mbarek, Hamdi ; McIntosh, Andrew M. ; McQueen, Matthew B. ; Meyers, Jacquelyn L. ; Milaneschi, Yuri ; Palviainen, Teemu ; Pearson, John F. ; Peterson, Roseann E. ; Ripatti, Samuli ; Ryu, Euijung ; Saccone, Nancy L. ; Salvatore, Jessica E. ; Sanchez-Roige, Sandra ; Schwandt, Melanie ; Sherva, Richard ; Streit, Fabian ; Strohmaier, Jana ; Thomas, Nathaniel ; Wang, Jen-Chyong ; Webb, Bradley T. ; Wedow, Robbee ; Wetherill, Leah ; Wills, Amanda G. ; Boardman, Jason D. ; Chen, Danfeng ; Choi, Doo-Sup ; Copeland, William E. ; Culverhouse, Robert C. ; Dahmen, Norbert ; Degenhardt, Louisa ; Domingue, Benjamin W. ; Elson, Sarah L. ; Frye, Mark A. ; Gäbel, Wolfgang ; Hayward, Caroline ; Ising, Marcus ; Keyes, Margaret ; Kiefer, Falk ; Kramer, John ; Kuperman, Samuel ; Lucae, Susanne ; Lynskey, Michael T. ; Maier, Wolfgang ; Mann, Karl ; Männistö, Satu ; Müller-Myhsok, Bertram ; Murray, Alison D. ; Nurnberger, John I. ; Palotie, Aarno ; Preuss, Ulrich ; Räikkönen, Katri ; Reynolds, Maureen D. ; Ridinger, Monika ; Scherbaum, Norbert ; Schuckit, Marc A. ; Soyka, Michael ; Treutlein, Jens ; Witt, Stephanie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-pubmedcentral_primary_oai_pubmedcentral_nih_gov_64302073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Walters, Raymond K.</creatorcontrib><creatorcontrib>Polimanti, Renato</creatorcontrib><creatorcontrib>Johnson, Emma C.</creatorcontrib><creatorcontrib>McClintick, Jeanette N.</creatorcontrib><creatorcontrib>Adams, Mark J.</creatorcontrib><creatorcontrib>Adkins, Amy E.</creatorcontrib><creatorcontrib>Aliev, Fazil</creatorcontrib><creatorcontrib>Bacanu, Silviu-Alin</creatorcontrib><creatorcontrib>Batzler, Anthony</creatorcontrib><creatorcontrib>Bertelsen, Sarah</creatorcontrib><creatorcontrib>Biernacka, Joanna M.</creatorcontrib><creatorcontrib>Bigdeli, Tim B.</creatorcontrib><creatorcontrib>Chen, Li-Shiun</creatorcontrib><creatorcontrib>Clarke, Toni-Kim</creatorcontrib><creatorcontrib>Chou, Yi-Ling</creatorcontrib><creatorcontrib>Degenhardt, Franziska</creatorcontrib><creatorcontrib>Docherty, Anna R.</creatorcontrib><creatorcontrib>Edwards, Alexis C.</creatorcontrib><creatorcontrib>Fontanillas, Pierre</creatorcontrib><creatorcontrib>Foo, Jerome C.</creatorcontrib><creatorcontrib>Fox, Louis</creatorcontrib><creatorcontrib>Frank, Josef</creatorcontrib><creatorcontrib>Giegling, Ina</creatorcontrib><creatorcontrib>Gordon, Scott</creatorcontrib><creatorcontrib>Hack, Laura M.</creatorcontrib><creatorcontrib>Hartmann, Annette M.</creatorcontrib><creatorcontrib>Hartz, Sarah M.</creatorcontrib><creatorcontrib>Heilmann-Heimbach, Stefanie</creatorcontrib><creatorcontrib>Herms, Stefan</creatorcontrib><creatorcontrib>Hodgkinson, Colin</creatorcontrib><creatorcontrib>Hoffmann, Per</creatorcontrib><creatorcontrib>Hottenga, Jouke Jan</creatorcontrib><creatorcontrib>Kennedy, Martin A.</creatorcontrib><creatorcontrib>Alanne-Kinnunen, Mervi</creatorcontrib><creatorcontrib>Konte, Bettina</creatorcontrib><creatorcontrib>Lahti, Jari</creatorcontrib><creatorcontrib>Lahti-Pulkkinen, Marius</creatorcontrib><creatorcontrib>Lai, Dongbing</creatorcontrib><creatorcontrib>Ligthart, Lannie</creatorcontrib><creatorcontrib>Loukola, Anu</creatorcontrib><creatorcontrib>Maher, Brion S.</creatorcontrib><creatorcontrib>Mbarek, Hamdi</creatorcontrib><creatorcontrib>McIntosh, Andrew M.</creatorcontrib><creatorcontrib>McQueen, Matthew B.</creatorcontrib><creatorcontrib>Meyers, Jacquelyn L.</creatorcontrib><creatorcontrib>Milaneschi, Yuri</creatorcontrib><creatorcontrib>Palviainen, Teemu</creatorcontrib><creatorcontrib>Pearson, John F.</creatorcontrib><creatorcontrib>Peterson, Roseann E.</creatorcontrib><creatorcontrib>Ripatti, Samuli</creatorcontrib><creatorcontrib>Ryu, Euijung</creatorcontrib><creatorcontrib>Saccone, Nancy L.</creatorcontrib><creatorcontrib>Salvatore, Jessica E.</creatorcontrib><creatorcontrib>Sanchez-Roige, Sandra</creatorcontrib><creatorcontrib>Schwandt, Melanie</creatorcontrib><creatorcontrib>Sherva, Richard</creatorcontrib><creatorcontrib>Streit, Fabian</creatorcontrib><creatorcontrib>Strohmaier, Jana</creatorcontrib><creatorcontrib>Thomas, Nathaniel</creatorcontrib><creatorcontrib>Wang, Jen-Chyong</creatorcontrib><creatorcontrib>Webb, Bradley T.</creatorcontrib><creatorcontrib>Wedow, Robbee</creatorcontrib><creatorcontrib>Wetherill, Leah</creatorcontrib><creatorcontrib>Wills, Amanda G.</creatorcontrib><creatorcontrib>Boardman, Jason D.</creatorcontrib><creatorcontrib>Chen, Danfeng</creatorcontrib><creatorcontrib>Choi, Doo-Sup</creatorcontrib><creatorcontrib>Copeland, William E.</creatorcontrib><creatorcontrib>Culverhouse, Robert C.</creatorcontrib><creatorcontrib>Dahmen, Norbert</creatorcontrib><creatorcontrib>Degenhardt, Louisa</creatorcontrib><creatorcontrib>Domingue, Benjamin W.</creatorcontrib><creatorcontrib>Elson, Sarah L.</creatorcontrib><creatorcontrib>Frye, Mark A.</creatorcontrib><creatorcontrib>Gäbel, Wolfgang</creatorcontrib><creatorcontrib>Hayward, Caroline</creatorcontrib><creatorcontrib>Ising, Marcus</creatorcontrib><creatorcontrib>Keyes, Margaret</creatorcontrib><creatorcontrib>Kiefer, Falk</creatorcontrib><creatorcontrib>Kramer, John</creatorcontrib><creatorcontrib>Kuperman, Samuel</creatorcontrib><creatorcontrib>Lucae, Susanne</creatorcontrib><creatorcontrib>Lynskey, Michael T.</creatorcontrib><creatorcontrib>Maier, Wolfgang</creatorcontrib><creatorcontrib>Mann, Karl</creatorcontrib><creatorcontrib>Männistö, Satu</creatorcontrib><creatorcontrib>Müller-Myhsok, Bertram</creatorcontrib><creatorcontrib>Murray, Alison D.</creatorcontrib><creatorcontrib>Nurnberger, John I.</creatorcontrib><creatorcontrib>Palotie, Aarno</creatorcontrib><creatorcontrib>Preuss, Ulrich</creatorcontrib><creatorcontrib>Räikkönen, Katri</creatorcontrib><creatorcontrib>Reynolds, Maureen D.</creatorcontrib><creatorcontrib>Ridinger, Monika</creatorcontrib><creatorcontrib>Scherbaum, Norbert</creatorcontrib><creatorcontrib>Schuckit, Marc A.</creatorcontrib><creatorcontrib>Soyka, Michael</creatorcontrib><creatorcontrib>Treutlein, Jens</creatorcontrib><creatorcontrib>Witt, Stephanie</creatorcontrib><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Walters, Raymond K.</au><au>Polimanti, Renato</au><au>Johnson, Emma C.</au><au>McClintick, Jeanette N.</au><au>Adams, Mark J.</au><au>Adkins, Amy E.</au><au>Aliev, Fazil</au><au>Bacanu, Silviu-Alin</au><au>Batzler, Anthony</au><au>Bertelsen, Sarah</au><au>Biernacka, Joanna M.</au><au>Bigdeli, Tim B.</au><au>Chen, Li-Shiun</au><au>Clarke, Toni-Kim</au><au>Chou, Yi-Ling</au><au>Degenhardt, Franziska</au><au>Docherty, Anna R.</au><au>Edwards, Alexis C.</au><au>Fontanillas, Pierre</au><au>Foo, Jerome C.</au><au>Fox, Louis</au><au>Frank, Josef</au><au>Giegling, Ina</au><au>Gordon, Scott</au><au>Hack, Laura M.</au><au>Hartmann, Annette M.</au><au>Hartz, Sarah M.</au><au>Heilmann-Heimbach, Stefanie</au><au>Herms, Stefan</au><au>Hodgkinson, Colin</au><au>Hoffmann, Per</au><au>Hottenga, Jouke Jan</au><au>Kennedy, Martin A.</au><au>Alanne-Kinnunen, Mervi</au><au>Konte, Bettina</au><au>Lahti, Jari</au><au>Lahti-Pulkkinen, Marius</au><au>Lai, Dongbing</au><au>Ligthart, Lannie</au><au>Loukola, Anu</au><au>Maher, Brion S.</au><au>Mbarek, Hamdi</au><au>McIntosh, Andrew M.</au><au>McQueen, Matthew B.</au><au>Meyers, Jacquelyn L.</au><au>Milaneschi, Yuri</au><au>Palviainen, Teemu</au><au>Pearson, John F.</au><au>Peterson, Roseann E.</au><au>Ripatti, Samuli</au><au>Ryu, Euijung</au><au>Saccone, Nancy L.</au><au>Salvatore, Jessica E.</au><au>Sanchez-Roige, Sandra</au><au>Schwandt, Melanie</au><au>Sherva, Richard</au><au>Streit, Fabian</au><au>Strohmaier, Jana</au><au>Thomas, Nathaniel</au><au>Wang, Jen-Chyong</au><au>Webb, Bradley T.</au><au>Wedow, Robbee</au><au>Wetherill, Leah</au><au>Wills, Amanda G.</au><au>Boardman, Jason D.</au><au>Chen, Danfeng</au><au>Choi, Doo-Sup</au><au>Copeland, William E.</au><au>Culverhouse, Robert C.</au><au>Dahmen, Norbert</au><au>Degenhardt, Louisa</au><au>Domingue, Benjamin W.</au><au>Elson, Sarah L.</au><au>Frye, Mark A.</au><au>Gäbel, Wolfgang</au><au>Hayward, Caroline</au><au>Ising, Marcus</au><au>Keyes, Margaret</au><au>Kiefer, Falk</au><au>Kramer, John</au><au>Kuperman, Samuel</au><au>Lucae, Susanne</au><au>Lynskey, Michael T.</au><au>Maier, Wolfgang</au><au>Mann, Karl</au><au>Männistö, Satu</au><au>Müller-Myhsok, Bertram</au><au>Murray, Alison D.</au><au>Nurnberger, John I.</au><au>Palotie, Aarno</au><au>Preuss, Ulrich</au><au>Räikkönen, Katri</au><au>Reynolds, Maureen D.</au><au>Ridinger, Monika</au><au>Scherbaum, Norbert</au><au>Schuckit, Marc A.</au><au>Soyka, Michael</au><au>Treutlein, Jens</au><au>Witt, Stephanie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Trans-ancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders</atitle><jtitle>Nature neuroscience</jtitle><date>2018-11-26</date><risdate>2018</risdate><volume>21</volume><issue>12</issue><spage>1656</spage><epage>1669</epage><pages>1656-1669</pages><issn>1097-6256</issn><eissn>1546-1726</eissn><abstract>Liability to alcohol dependence (AD) is heritable, but little is known
about its complex polygenic architecture or its genetic relationship with other
disorders. To discover loci associated with AD and characterize the relationship
between AD and other psychiatric and behavioral outcomes, we carried out the
largest GWAS to date of DSM-IV diagnosed AD. Genome-wide data on 14,904
individuals with AD and 37,944 controls from 28 case/control and family-based
studies were meta-analyzed, stratified by genetic ancestry (European, N =
46,568; African; N = 6,280). Independent, genome-wide significant effects of
different
ADH1B
variants were identified in European
(rs1229984; p = 9.8E-13) and African ancestries (rs2066702; p = 2.2E-9).
Significant genetic correlations were observed with 17 phenotypes, including
schizophrenia, ADHD, depression, and use of cigarettes and cannabis. The genetic
underpinnings of AD only partially overlap with those for alcohol consumption,
underscoring the genetic distinction between pathological and non-pathological
drinking behaviors.</abstract><pmid>30482948</pmid><doi>10.1038/s41593-018-0275-1</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1097-6256 |
| ispartof | Nature neuroscience, 2018-11, Vol.21 (12), p.1656-1669 |
| issn | 1097-6256 1546-1726 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6430207 |
| source | Nature; SpringerLink Journals - AutoHoldings |
| title | Trans-ancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders |
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