Genomewide Association Study for Maximum Number of Alcoholic Drinks in European Americans and African Americans

Background We conducted a genomewide association study (GWAS) for maximum number of alcoholic drinks consumed in a 24‐hour period (“MaxDrinks”), in 2 independent samples comprised of over 9,500 subjects, following up on our GWAS for alcohol dependence (AD) in European Americans (EAs) and African Ame...

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Veröffentlicht in:Alcoholism, clinical and experimental research clinical and experimental research, 2015-07, Vol.39 (7), p.1137-1147
Hauptverfasser: Xu, Ke, Kranzler, Henry R., Sherva, Richard, Sartor, Carolyn E., Almasy, Laura, Koesterer, Ryan, Zhao, Hongyu, Farrer, Lindsay A., Gelernter, Joel
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container_end_page 1147
container_issue 7
container_start_page 1137
container_title Alcoholism, clinical and experimental research
container_volume 39
creator Xu, Ke
Kranzler, Henry R.
Sherva, Richard
Sartor, Carolyn E.
Almasy, Laura
Koesterer, Ryan
Zhao, Hongyu
Farrer, Lindsay A.
Gelernter, Joel
description Background We conducted a genomewide association study (GWAS) for maximum number of alcoholic drinks consumed in a 24‐hour period (“MaxDrinks”), in 2 independent samples comprised of over 9,500 subjects, following up on our GWAS for alcohol dependence (AD) in European Americans (EAs) and African Americans (AAs). Methods The samples included our GWAS samples (Yale‐UPenn) recruited for studies of the genetics of drug or AD, and a publicly available sample: the Study of Addiction: Genetics and Environment (SAGE). Genomewide association analysis was performed for ~890,000 single nucleotide polymorphisms (SNPs) using linear association random effects models. EAs and AAs were separately analyzed. Results The results confirmed significant associations of the well‐known functional loci at ADH1B with MaxDrinks in EAs (rs1229984 Arg48His p = 5.96 × 10−15) and AAs (rs2066702 Arg370Cys, p = 2.50 × 10−10). The region of significant association on chromosome 4 was extended to LOC100507053 in AAs but not EAs. We also identified potentially novel significant common SNPs for MaxDrinks in EAs in the Yale‐UPenn sample: rs1799876 at SERPINC1 on chromosome 1 (4.00 × 10−8) and rs2309169 close to ANKRD36 on chromosome 2 (p = 5.58 × 10−9). After adjusting for the peak SNP rs1229984 on ADH1B, rs1799876 was nearly significant (p = 1.99 × 10−7) and rs2309169 remained highly significant (2.12 × 10−9). Conclusions The results provide further support that ADH1B modulates alcohol consumption. Future replications of potential novel loci are warranted. This is the largest MaxDrinks GWAS to date, the first in AAs.
doi_str_mv 10.1111/acer.12751
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Methods The samples included our GWAS samples (Yale‐UPenn) recruited for studies of the genetics of drug or AD, and a publicly available sample: the Study of Addiction: Genetics and Environment (SAGE). Genomewide association analysis was performed for ~890,000 single nucleotide polymorphisms (SNPs) using linear association random effects models. EAs and AAs were separately analyzed. Results The results confirmed significant associations of the well‐known functional loci at ADH1B with MaxDrinks in EAs (rs1229984 Arg48His p = 5.96 × 10−15) and AAs (rs2066702 Arg370Cys, p = 2.50 × 10−10). The region of significant association on chromosome 4 was extended to LOC100507053 in AAs but not EAs. We also identified potentially novel significant common SNPs for MaxDrinks in EAs in the Yale‐UPenn sample: rs1799876 at SERPINC1 on chromosome 1 (4.00 × 10−8) and rs2309169 close to ANKRD36 on chromosome 2 (p = 5.58 × 10−9). After adjusting for the peak SNP rs1229984 on ADH1B, rs1799876 was nearly significant (p = 1.99 × 10−7) and rs2309169 remained highly significant (2.12 × 10−9). Conclusions The results provide further support that ADH1B modulates alcohol consumption. Future replications of potential novel loci are warranted. This is the largest MaxDrinks GWAS to date, the first in AAs.</description><identifier>ISSN: 0145-6008</identifier><identifier>ISSN: 1530-0277</identifier><identifier>EISSN: 1530-0277</identifier><identifier>DOI: 10.1111/acer.12751</identifier><identifier>PMID: 26036284</identifier><identifier>CODEN: ACRSDM</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>African American ; Alcohol Dehydrogenase - genetics ; Alcohol Drinking - ethnology ; Alcohol Drinking - genetics ; Alcohol Maximum Drinks ; Black or African American - statistics &amp; numerical data ; European American ; Genome-Wide Association Study ; Genomewide Association ; Humans ; White People - statistics &amp; numerical data</subject><ispartof>Alcoholism, clinical and experimental research, 2015-07, Vol.39 (7), p.1137-1147</ispartof><rights>Copyright © 2015 by the Research Society on Alcoholism</rights><rights>Copyright © 2015 by the Research Society on Alcoholism.</rights><rights>2015 Research Society on Alcoholism</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5011-2e0e5b4604a4a87605c3da15e64ce58f4ce5eccda98e4b7c53ea54e7a0f49b2c3</citedby><cites>FETCH-LOGICAL-c5011-2e0e5b4604a4a87605c3da15e64ce58f4ce5eccda98e4b7c53ea54e7a0f49b2c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Facer.12751$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Facer.12751$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26036284$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xu, Ke</creatorcontrib><creatorcontrib>Kranzler, Henry R.</creatorcontrib><creatorcontrib>Sherva, Richard</creatorcontrib><creatorcontrib>Sartor, Carolyn E.</creatorcontrib><creatorcontrib>Almasy, Laura</creatorcontrib><creatorcontrib>Koesterer, Ryan</creatorcontrib><creatorcontrib>Zhao, Hongyu</creatorcontrib><creatorcontrib>Farrer, Lindsay A.</creatorcontrib><creatorcontrib>Gelernter, Joel</creatorcontrib><title>Genomewide Association Study for Maximum Number of Alcoholic Drinks in European Americans and African Americans</title><title>Alcoholism, clinical and experimental research</title><addtitle>Alcohol Clin Exp Res</addtitle><description>Background We conducted a genomewide association study (GWAS) for maximum number of alcoholic drinks consumed in a 24‐hour period (“MaxDrinks”), in 2 independent samples comprised of over 9,500 subjects, following up on our GWAS for alcohol dependence (AD) in European Americans (EAs) and African Americans (AAs). Methods The samples included our GWAS samples (Yale‐UPenn) recruited for studies of the genetics of drug or AD, and a publicly available sample: the Study of Addiction: Genetics and Environment (SAGE). Genomewide association analysis was performed for ~890,000 single nucleotide polymorphisms (SNPs) using linear association random effects models. EAs and AAs were separately analyzed. Results The results confirmed significant associations of the well‐known functional loci at ADH1B with MaxDrinks in EAs (rs1229984 Arg48His p = 5.96 × 10−15) and AAs (rs2066702 Arg370Cys, p = 2.50 × 10−10). The region of significant association on chromosome 4 was extended to LOC100507053 in AAs but not EAs. We also identified potentially novel significant common SNPs for MaxDrinks in EAs in the Yale‐UPenn sample: rs1799876 at SERPINC1 on chromosome 1 (4.00 × 10−8) and rs2309169 close to ANKRD36 on chromosome 2 (p = 5.58 × 10−9). After adjusting for the peak SNP rs1229984 on ADH1B, rs1799876 was nearly significant (p = 1.99 × 10−7) and rs2309169 remained highly significant (2.12 × 10−9). Conclusions The results provide further support that ADH1B modulates alcohol consumption. Future replications of potential novel loci are warranted. This is the largest MaxDrinks GWAS to date, the first in AAs.</description><subject>African American</subject><subject>Alcohol Dehydrogenase - genetics</subject><subject>Alcohol Drinking - ethnology</subject><subject>Alcohol Drinking - genetics</subject><subject>Alcohol Maximum Drinks</subject><subject>Black or African American - statistics &amp; numerical data</subject><subject>European American</subject><subject>Genome-Wide Association Study</subject><subject>Genomewide Association</subject><subject>Humans</subject><subject>White People - statistics &amp; numerical data</subject><issn>0145-6008</issn><issn>1530-0277</issn><issn>1530-0277</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1v1DAQhi1ERZfChR-ALHFBSGnHiT-SY7rdLlRtQXwIbpbjTITbxF7sjdr998122yJxYA4zmtEzr0bzEvKGwSGb4shYjIcsV4I9IzMmCsggV-o5mQHjIpMA5T55mdIVAPBSyhdkP5dQyLzkMxKW6MOAN65FWqcUrDNrFzz9th7bDe1CpBfm1g3jQC_HocFIQ0fr3obfoXeWnkTnrxN1ni7GGFZoPK0HjM4an6jxLa27--bv9BXZ60yf8PVDPSA_Thff5x-z88_LT_P6PLMCGMtyBBQNl8ANN6WSIGzRGiZQcoui7LYZrW1NVSJvlBUFGsFRGeh41eS2OCDvd7qrGP6MmNZ6cMli3xuPYUyayapQIKtcTei7f9CrMEY_Xbel8hIqJcVEfdhRNoaUInZ6Fd1g4kYz0Fsb9NYGfW_DBL99kBybAdsn9PHvE8B2wI3rcfMfKV3PF18fRbPdjktrvH3aMfFaS1UooX9eLrX4xcQZO_mij4s70hOhow</recordid><startdate>201507</startdate><enddate>201507</enddate><creator>Xu, Ke</creator><creator>Kranzler, Henry R.</creator><creator>Sherva, Richard</creator><creator>Sartor, Carolyn E.</creator><creator>Almasy, Laura</creator><creator>Koesterer, Ryan</creator><creator>Zhao, Hongyu</creator><creator>Farrer, Lindsay A.</creator><creator>Gelernter, Joel</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</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>7TK</scope><scope>K7.</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>201507</creationdate><title>Genomewide Association Study for Maximum Number of Alcoholic Drinks in European Americans and African Americans</title><author>Xu, Ke ; Kranzler, Henry R. ; Sherva, Richard ; Sartor, Carolyn E. ; Almasy, Laura ; Koesterer, Ryan ; Zhao, Hongyu ; Farrer, Lindsay A. ; Gelernter, Joel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5011-2e0e5b4604a4a87605c3da15e64ce58f4ce5eccda98e4b7c53ea54e7a0f49b2c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>African American</topic><topic>Alcohol Dehydrogenase - genetics</topic><topic>Alcohol Drinking - ethnology</topic><topic>Alcohol Drinking - genetics</topic><topic>Alcohol Maximum Drinks</topic><topic>Black or African American - statistics &amp; numerical data</topic><topic>European American</topic><topic>Genome-Wide Association Study</topic><topic>Genomewide Association</topic><topic>Humans</topic><topic>White People - statistics &amp; numerical data</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xu, Ke</creatorcontrib><creatorcontrib>Kranzler, Henry R.</creatorcontrib><creatorcontrib>Sherva, Richard</creatorcontrib><creatorcontrib>Sartor, Carolyn E.</creatorcontrib><creatorcontrib>Almasy, Laura</creatorcontrib><creatorcontrib>Koesterer, Ryan</creatorcontrib><creatorcontrib>Zhao, Hongyu</creatorcontrib><creatorcontrib>Farrer, Lindsay A.</creatorcontrib><creatorcontrib>Gelernter, Joel</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Criminal Justice (Alumni)</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Alcoholism, clinical and experimental research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xu, Ke</au><au>Kranzler, Henry R.</au><au>Sherva, Richard</au><au>Sartor, Carolyn E.</au><au>Almasy, Laura</au><au>Koesterer, Ryan</au><au>Zhao, Hongyu</au><au>Farrer, Lindsay A.</au><au>Gelernter, Joel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genomewide Association Study for Maximum Number of Alcoholic Drinks in European Americans and African Americans</atitle><jtitle>Alcoholism, clinical and experimental research</jtitle><addtitle>Alcohol Clin Exp Res</addtitle><date>2015-07</date><risdate>2015</risdate><volume>39</volume><issue>7</issue><spage>1137</spage><epage>1147</epage><pages>1137-1147</pages><issn>0145-6008</issn><issn>1530-0277</issn><eissn>1530-0277</eissn><coden>ACRSDM</coden><abstract>Background We conducted a genomewide association study (GWAS) for maximum number of alcoholic drinks consumed in a 24‐hour period (“MaxDrinks”), in 2 independent samples comprised of over 9,500 subjects, following up on our GWAS for alcohol dependence (AD) in European Americans (EAs) and African Americans (AAs). Methods The samples included our GWAS samples (Yale‐UPenn) recruited for studies of the genetics of drug or AD, and a publicly available sample: the Study of Addiction: Genetics and Environment (SAGE). Genomewide association analysis was performed for ~890,000 single nucleotide polymorphisms (SNPs) using linear association random effects models. EAs and AAs were separately analyzed. Results The results confirmed significant associations of the well‐known functional loci at ADH1B with MaxDrinks in EAs (rs1229984 Arg48His p = 5.96 × 10−15) and AAs (rs2066702 Arg370Cys, p = 2.50 × 10−10). The region of significant association on chromosome 4 was extended to LOC100507053 in AAs but not EAs. We also identified potentially novel significant common SNPs for MaxDrinks in EAs in the Yale‐UPenn sample: rs1799876 at SERPINC1 on chromosome 1 (4.00 × 10−8) and rs2309169 close to ANKRD36 on chromosome 2 (p = 5.58 × 10−9). After adjusting for the peak SNP rs1229984 on ADH1B, rs1799876 was nearly significant (p = 1.99 × 10−7) and rs2309169 remained highly significant (2.12 × 10−9). Conclusions The results provide further support that ADH1B modulates alcohol consumption. Future replications of potential novel loci are warranted. This is the largest MaxDrinks GWAS to date, the first in AAs.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>26036284</pmid><doi>10.1111/acer.12751</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record>
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subjects African American
Alcohol Dehydrogenase - genetics
Alcohol Drinking - ethnology
Alcohol Drinking - genetics
Alcohol Maximum Drinks
Black or African American - statistics & numerical data
European American
Genome-Wide Association Study
Genomewide Association
Humans
White People - statistics & numerical data
title Genomewide Association Study for Maximum Number of Alcoholic Drinks in European Americans and African Americans
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