Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat
Background: To identify loci associated with abdominal fat and replicate prior findings, we performed genome-wide association (GWA) studies of abdominal fat traits: subcutaneous adipose tissue (SAT); visceral adipose tissue (VAT); total adipose tissue (TAT) and visceral to subcutaneous adipose tissu...
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| Veröffentlicht in: | International Journal of Obesity 2016-04, Vol.40 (4), p.662-674 |
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| creator | Sung, Y J Pérusse, L Sarzynski, M A Fornage, M Sidney, S Sternfeld, B Rice, T Terry, J G Jacobs, D R Katzmarzyk, P Curran, J E Jeffrey Carr, J Blangero, J Ghosh, S Després, J-P Rankinen, T Rao, D C Bouchard, C |
| description | Background:
To identify loci associated with abdominal fat and replicate prior findings, we performed genome-wide association (GWA) studies of abdominal fat traits: subcutaneous adipose tissue (SAT); visceral adipose tissue (VAT); total adipose tissue (TAT) and visceral to subcutaneous adipose tissue ratio (VSR).
Subjects and Methods:
Sex-combined and sex-stratified analyses were performed on each trait with (TRAIT–BMI) or without (TRAIT) adjustment for body mass index (BMI), and cohort-specific results were combined via a fixed effects meta-analysis. A total of 2513 subjects of European descent were available for the discovery phase. For replication, 2171 European Americans and 772 African Americans were available.
Results:
A total of 52 single-nucleotide polymorphisms (SNPs) encompassing 7 loci showed suggestive evidence of association (
P |
| doi_str_mv | 10.1038/ijo.2015.217 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4821694</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A451940709</galeid><sourcerecordid>A451940709</sourcerecordid><originalsourceid>FETCH-LOGICAL-c609t-56714d64e8bf311d0404fa572abc88b380cdacade8060af705c88b73e41007473</originalsourceid><addsrcrecordid>eNp9ks-L1DAUx4Mo7rh68ywFQTzY8aVNmvSysCy6Cgte9BzS5LWToU3Gpt3V_950Zx1mZPEUkvd5P77fPEJeU1hTKOVHtw3rAihfF1Q8ISvKRJVzVounZAUliBx4xc_Iixi3AMA5FM_JWVExCXUBK2Kv0YcB8ztnMdMxBuP05ILP4jRbhzGLc9dhnLKIv_K4Q-NaZ7I-YQcabXbnpk2mGxsG53WfaW-zWxcNjunS6ukledbqPuKrh_Oc_Pj86fvVl_zm2_XXq8ub3FRQTzmvBGW2YiibtqTUAgPWai4K3Rgpm1KCsdpoixIq0K0AvjyLEhkFEEyU5-RiX3c3NwNag35KE6jd6AY9_lZBO3Ua8W6junCrmCxoVbNU4P1DgTH8nJNsNSwy-l57DHNUVEjgyef7Xm__QbdhHpP6qIqqrGlZ0LL-H0WFkAxAsiOq0z0q59uQpjNLa3XJOK0ZCFio9SPUvSGDM8Fj69L7ScK7o4QN6n7axNDPy__GU_DDHjRjiHHE9mAZBbUsmUpLppYlU0l8wt8c23yA_25VAvI9EFPIdzgeqX6s4B_5vtox</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1778400849</pqid></control><display><type>article</type><title>Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat</title><source>MEDLINE</source><source>SpringerLink Journals</source><source>Nature Journals Online</source><creator>Sung, Y J ; Pérusse, L ; Sarzynski, M A ; Fornage, M ; Sidney, S ; Sternfeld, B ; Rice, T ; Terry, J G ; Jacobs, D R ; Katzmarzyk, P ; Curran, J E ; Jeffrey Carr, J ; Blangero, J ; Ghosh, S ; Després, J-P ; Rankinen, T ; Rao, D C ; Bouchard, C</creator><creatorcontrib>Sung, Y J ; Pérusse, L ; Sarzynski, M A ; Fornage, M ; Sidney, S ; Sternfeld, B ; Rice, T ; Terry, J G ; Jacobs, D R ; Katzmarzyk, P ; Curran, J E ; Jeffrey Carr, J ; Blangero, J ; Ghosh, S ; Després, J-P ; Rankinen, T ; Rao, D C ; Bouchard, C</creatorcontrib><description>Background:
To identify loci associated with abdominal fat and replicate prior findings, we performed genome-wide association (GWA) studies of abdominal fat traits: subcutaneous adipose tissue (SAT); visceral adipose tissue (VAT); total adipose tissue (TAT) and visceral to subcutaneous adipose tissue ratio (VSR).
Subjects and Methods:
Sex-combined and sex-stratified analyses were performed on each trait with (TRAIT–BMI) or without (TRAIT) adjustment for body mass index (BMI), and cohort-specific results were combined via a fixed effects meta-analysis. A total of 2513 subjects of European descent were available for the discovery phase. For replication, 2171 European Americans and 772 African Americans were available.
Results:
A total of 52 single-nucleotide polymorphisms (SNPs) encompassing 7 loci showed suggestive evidence of association (
P
<1.0 × 10
−6
) with abdominal fat in the sex-combined analyses. The strongest evidence was found on chromosome 7p14.3 between a SNP near
BBS9
gene and VAT (rs12374818;
P
=1.10 × 10
−7
), an association that was replicated (
P
=0.02). For the BMI-adjusted trait, the strongest evidence of association was found between a SNP near
CYCSP30
and VAT–BMI (rs10506943;
P
=2.42 × 10
−7
). Our sex-specific analyses identified one genome-wide significant (
P
<5.0 × 10
−8
) locus for SAT in women with 11 SNPs encompassing the
MLLT10, DNAJC1
and
EBLN1
genes on chromosome 10p12.31 (
P
=3.97 × 10
–8
to 1.13 × 10
−8
). The
THNSL2
gene previously associated with VAT in women was also replicated (
P
=0.006). The six gene/loci showing the strongest evidence of association with VAT or VAT-BMI were interrogated for their functional links with obesity and inflammation using the Biograph knowledge-mining software. Genes showing the closest functional links with obesity and inflammation were
ADCY8
and
KCNK9
, respectively.
Conclusions:
Our results provide evidence for new loci influencing abdominal visceral (
BBS9, ADCY8, KCNK9
) and subcutaneous (
MLLT10/DNAJC1/EBLN1
) fat, and confirmed a locus (
THNSL2
) previously reported to be associated with abdominal fat in women.</description><identifier>ISSN: 0307-0565</identifier><identifier>EISSN: 1476-5497</identifier><identifier>DOI: 10.1038/ijo.2015.217</identifier><identifier>PMID: 26480920</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>45 ; 45/43 ; 59 ; 59/57 ; 631/208 ; 631/208/205/2138 ; 692/499 ; 692/699/2743/393 ; 692/700/139/2818 ; Abdomen ; Adipose tissue ; Adipose tissues ; Adult ; Analysis ; Black or African American - genetics ; Body fat ; Body Mass Index ; Body size ; Cardiovascular Diseases - etiology ; Cardiovascular Diseases - genetics ; Cardiovascular Diseases - physiopathology ; Chromosome 10 ; Chromosome 7 ; Chromosomes ; Epidemiology ; Female ; Genes ; Genetic Predisposition to Disease - genetics ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Health Promotion and Disease Prevention ; Humans ; Inflammation ; Internal Medicine ; Intra-Abdominal Fat - metabolism ; Loci ; Male ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Middle Aged ; Nucleotides ; Obesity ; original-article ; Phenotype ; Polymorphism, Single Nucleotide - genetics ; Potassium channels ; Public Health ; Sex ; Sex Characteristics ; Sex Factors ; Single-nucleotide polymorphism ; Subcutaneous Fat, Abdominal - metabolism ; Systematic review ; United States ; White People - genetics</subject><ispartof>International Journal of Obesity, 2016-04, Vol.40 (4), p.662-674</ispartof><rights>Macmillan Publishers Limited 2016</rights><rights>COPYRIGHT 2016 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Apr 2016</rights><rights>Macmillan Publishers Limited 2016.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c609t-56714d64e8bf311d0404fa572abc88b380cdacade8060af705c88b73e41007473</citedby><cites>FETCH-LOGICAL-c609t-56714d64e8bf311d0404fa572abc88b380cdacade8060af705c88b73e41007473</cites><orcidid>0000-0002-4398-8237</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ijo.2015.217$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/ijo.2015.217$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26480920$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sung, Y J</creatorcontrib><creatorcontrib>Pérusse, L</creatorcontrib><creatorcontrib>Sarzynski, M A</creatorcontrib><creatorcontrib>Fornage, M</creatorcontrib><creatorcontrib>Sidney, S</creatorcontrib><creatorcontrib>Sternfeld, B</creatorcontrib><creatorcontrib>Rice, T</creatorcontrib><creatorcontrib>Terry, J G</creatorcontrib><creatorcontrib>Jacobs, D R</creatorcontrib><creatorcontrib>Katzmarzyk, P</creatorcontrib><creatorcontrib>Curran, J E</creatorcontrib><creatorcontrib>Jeffrey Carr, J</creatorcontrib><creatorcontrib>Blangero, J</creatorcontrib><creatorcontrib>Ghosh, S</creatorcontrib><creatorcontrib>Després, J-P</creatorcontrib><creatorcontrib>Rankinen, T</creatorcontrib><creatorcontrib>Rao, D C</creatorcontrib><creatorcontrib>Bouchard, C</creatorcontrib><title>Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat</title><title>International Journal of Obesity</title><addtitle>Int J Obes</addtitle><addtitle>Int J Obes (Lond)</addtitle><description>Background:
To identify loci associated with abdominal fat and replicate prior findings, we performed genome-wide association (GWA) studies of abdominal fat traits: subcutaneous adipose tissue (SAT); visceral adipose tissue (VAT); total adipose tissue (TAT) and visceral to subcutaneous adipose tissue ratio (VSR).
Subjects and Methods:
Sex-combined and sex-stratified analyses were performed on each trait with (TRAIT–BMI) or without (TRAIT) adjustment for body mass index (BMI), and cohort-specific results were combined via a fixed effects meta-analysis. A total of 2513 subjects of European descent were available for the discovery phase. For replication, 2171 European Americans and 772 African Americans were available.
Results:
A total of 52 single-nucleotide polymorphisms (SNPs) encompassing 7 loci showed suggestive evidence of association (
P
<1.0 × 10
−6
) with abdominal fat in the sex-combined analyses. The strongest evidence was found on chromosome 7p14.3 between a SNP near
BBS9
gene and VAT (rs12374818;
P
=1.10 × 10
−7
), an association that was replicated (
P
=0.02). For the BMI-adjusted trait, the strongest evidence of association was found between a SNP near
CYCSP30
and VAT–BMI (rs10506943;
P
=2.42 × 10
−7
). Our sex-specific analyses identified one genome-wide significant (
P
<5.0 × 10
−8
) locus for SAT in women with 11 SNPs encompassing the
MLLT10, DNAJC1
and
EBLN1
genes on chromosome 10p12.31 (
P
=3.97 × 10
–8
to 1.13 × 10
−8
). The
THNSL2
gene previously associated with VAT in women was also replicated (
P
=0.006). The six gene/loci showing the strongest evidence of association with VAT or VAT-BMI were interrogated for their functional links with obesity and inflammation using the Biograph knowledge-mining software. Genes showing the closest functional links with obesity and inflammation were
ADCY8
and
KCNK9
, respectively.
Conclusions:
Our results provide evidence for new loci influencing abdominal visceral (
BBS9, ADCY8, KCNK9
) and subcutaneous (
MLLT10/DNAJC1/EBLN1
) fat, and confirmed a locus (
THNSL2
) previously reported to be associated with abdominal fat in women.</description><subject>45</subject><subject>45/43</subject><subject>59</subject><subject>59/57</subject><subject>631/208</subject><subject>631/208/205/2138</subject><subject>692/499</subject><subject>692/699/2743/393</subject><subject>692/700/139/2818</subject><subject>Abdomen</subject><subject>Adipose tissue</subject><subject>Adipose tissues</subject><subject>Adult</subject><subject>Analysis</subject><subject>Black or African American - genetics</subject><subject>Body fat</subject><subject>Body Mass Index</subject><subject>Body size</subject><subject>Cardiovascular Diseases - etiology</subject><subject>Cardiovascular Diseases - genetics</subject><subject>Cardiovascular Diseases - physiopathology</subject><subject>Chromosome 10</subject><subject>Chromosome 7</subject><subject>Chromosomes</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Genes</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Health Promotion and Disease Prevention</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Internal Medicine</subject><subject>Intra-Abdominal Fat - metabolism</subject><subject>Loci</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Middle Aged</subject><subject>Nucleotides</subject><subject>Obesity</subject><subject>original-article</subject><subject>Phenotype</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Potassium channels</subject><subject>Public Health</subject><subject>Sex</subject><subject>Sex Characteristics</subject><subject>Sex Factors</subject><subject>Single-nucleotide polymorphism</subject><subject>Subcutaneous Fat, Abdominal - metabolism</subject><subject>Systematic review</subject><subject>United States</subject><subject>White People - genetics</subject><issn>0307-0565</issn><issn>1476-5497</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9ks-L1DAUx4Mo7rh68ywFQTzY8aVNmvSysCy6Cgte9BzS5LWToU3Gpt3V_950Zx1mZPEUkvd5P77fPEJeU1hTKOVHtw3rAihfF1Q8ISvKRJVzVounZAUliBx4xc_Iixi3AMA5FM_JWVExCXUBK2Kv0YcB8ztnMdMxBuP05ILP4jRbhzGLc9dhnLKIv_K4Q-NaZ7I-YQcabXbnpk2mGxsG53WfaW-zWxcNjunS6ukledbqPuKrh_Oc_Pj86fvVl_zm2_XXq8ub3FRQTzmvBGW2YiibtqTUAgPWai4K3Rgpm1KCsdpoixIq0K0AvjyLEhkFEEyU5-RiX3c3NwNag35KE6jd6AY9_lZBO3Ua8W6junCrmCxoVbNU4P1DgTH8nJNsNSwy-l57DHNUVEjgyef7Xm__QbdhHpP6qIqqrGlZ0LL-H0WFkAxAsiOq0z0q59uQpjNLa3XJOK0ZCFio9SPUvSGDM8Fj69L7ScK7o4QN6n7axNDPy__GU_DDHjRjiHHE9mAZBbUsmUpLppYlU0l8wt8c23yA_25VAvI9EFPIdzgeqX6s4B_5vtox</recordid><startdate>20160401</startdate><enddate>20160401</enddate><creator>Sung, Y J</creator><creator>Pérusse, L</creator><creator>Sarzynski, M A</creator><creator>Fornage, M</creator><creator>Sidney, S</creator><creator>Sternfeld, B</creator><creator>Rice, T</creator><creator>Terry, J G</creator><creator>Jacobs, D R</creator><creator>Katzmarzyk, P</creator><creator>Curran, J E</creator><creator>Jeffrey Carr, J</creator><creator>Blangero, J</creator><creator>Ghosh, S</creator><creator>Després, J-P</creator><creator>Rankinen, T</creator><creator>Rao, D C</creator><creator>Bouchard, C</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><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>3V.</scope><scope>7T2</scope><scope>7TK</scope><scope>7TS</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7U2</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-4398-8237</orcidid></search><sort><creationdate>20160401</creationdate><title>Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat</title><author>Sung, Y J ; Pérusse, L ; Sarzynski, M A ; Fornage, M ; Sidney, S ; Sternfeld, B ; Rice, T ; Terry, J G ; Jacobs, D R ; Katzmarzyk, P ; Curran, J E ; Jeffrey Carr, J ; Blangero, J ; Ghosh, S ; Després, J-P ; Rankinen, T ; Rao, D C ; Bouchard, C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c609t-56714d64e8bf311d0404fa572abc88b380cdacade8060af705c88b73e41007473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>45</topic><topic>45/43</topic><topic>59</topic><topic>59/57</topic><topic>631/208</topic><topic>631/208/205/2138</topic><topic>692/499</topic><topic>692/699/2743/393</topic><topic>692/700/139/2818</topic><topic>Abdomen</topic><topic>Adipose tissue</topic><topic>Adipose tissues</topic><topic>Adult</topic><topic>Analysis</topic><topic>Black or African American - genetics</topic><topic>Body fat</topic><topic>Body Mass Index</topic><topic>Body size</topic><topic>Cardiovascular Diseases - etiology</topic><topic>Cardiovascular Diseases - genetics</topic><topic>Cardiovascular Diseases - physiopathology</topic><topic>Chromosome 10</topic><topic>Chromosome 7</topic><topic>Chromosomes</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Genes</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Health Promotion and Disease Prevention</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Internal Medicine</topic><topic>Intra-Abdominal Fat - metabolism</topic><topic>Loci</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>Middle Aged</topic><topic>Nucleotides</topic><topic>Obesity</topic><topic>original-article</topic><topic>Phenotype</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Potassium channels</topic><topic>Public Health</topic><topic>Sex</topic><topic>Sex Characteristics</topic><topic>Sex Factors</topic><topic>Single-nucleotide polymorphism</topic><topic>Subcutaneous Fat, Abdominal - metabolism</topic><topic>Systematic review</topic><topic>United States</topic><topic>White People - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sung, Y J</creatorcontrib><creatorcontrib>Pérusse, L</creatorcontrib><creatorcontrib>Sarzynski, M A</creatorcontrib><creatorcontrib>Fornage, M</creatorcontrib><creatorcontrib>Sidney, S</creatorcontrib><creatorcontrib>Sternfeld, B</creatorcontrib><creatorcontrib>Rice, T</creatorcontrib><creatorcontrib>Terry, J G</creatorcontrib><creatorcontrib>Jacobs, D R</creatorcontrib><creatorcontrib>Katzmarzyk, P</creatorcontrib><creatorcontrib>Curran, J E</creatorcontrib><creatorcontrib>Jeffrey Carr, J</creatorcontrib><creatorcontrib>Blangero, J</creatorcontrib><creatorcontrib>Ghosh, S</creatorcontrib><creatorcontrib>Després, J-P</creatorcontrib><creatorcontrib>Rankinen, T</creatorcontrib><creatorcontrib>Rao, D C</creatorcontrib><creatorcontrib>Bouchard, C</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Physical Education Index</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>Safety Science and Risk</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International Journal of Obesity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sung, Y J</au><au>Pérusse, L</au><au>Sarzynski, M A</au><au>Fornage, M</au><au>Sidney, S</au><au>Sternfeld, B</au><au>Rice, T</au><au>Terry, J G</au><au>Jacobs, D R</au><au>Katzmarzyk, P</au><au>Curran, J E</au><au>Jeffrey Carr, J</au><au>Blangero, J</au><au>Ghosh, S</au><au>Després, J-P</au><au>Rankinen, T</au><au>Rao, D C</au><au>Bouchard, C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat</atitle><jtitle>International Journal of Obesity</jtitle><stitle>Int J Obes</stitle><addtitle>Int J Obes (Lond)</addtitle><date>2016-04-01</date><risdate>2016</risdate><volume>40</volume><issue>4</issue><spage>662</spage><epage>674</epage><pages>662-674</pages><issn>0307-0565</issn><eissn>1476-5497</eissn><abstract>Background:
To identify loci associated with abdominal fat and replicate prior findings, we performed genome-wide association (GWA) studies of abdominal fat traits: subcutaneous adipose tissue (SAT); visceral adipose tissue (VAT); total adipose tissue (TAT) and visceral to subcutaneous adipose tissue ratio (VSR).
Subjects and Methods:
Sex-combined and sex-stratified analyses were performed on each trait with (TRAIT–BMI) or without (TRAIT) adjustment for body mass index (BMI), and cohort-specific results were combined via a fixed effects meta-analysis. A total of 2513 subjects of European descent were available for the discovery phase. For replication, 2171 European Americans and 772 African Americans were available.
Results:
A total of 52 single-nucleotide polymorphisms (SNPs) encompassing 7 loci showed suggestive evidence of association (
P
<1.0 × 10
−6
) with abdominal fat in the sex-combined analyses. The strongest evidence was found on chromosome 7p14.3 between a SNP near
BBS9
gene and VAT (rs12374818;
P
=1.10 × 10
−7
), an association that was replicated (
P
=0.02). For the BMI-adjusted trait, the strongest evidence of association was found between a SNP near
CYCSP30
and VAT–BMI (rs10506943;
P
=2.42 × 10
−7
). Our sex-specific analyses identified one genome-wide significant (
P
<5.0 × 10
−8
) locus for SAT in women with 11 SNPs encompassing the
MLLT10, DNAJC1
and
EBLN1
genes on chromosome 10p12.31 (
P
=3.97 × 10
–8
to 1.13 × 10
−8
). The
THNSL2
gene previously associated with VAT in women was also replicated (
P
=0.006). The six gene/loci showing the strongest evidence of association with VAT or VAT-BMI were interrogated for their functional links with obesity and inflammation using the Biograph knowledge-mining software. Genes showing the closest functional links with obesity and inflammation were
ADCY8
and
KCNK9
, respectively.
Conclusions:
Our results provide evidence for new loci influencing abdominal visceral (
BBS9, ADCY8, KCNK9
) and subcutaneous (
MLLT10/DNAJC1/EBLN1
) fat, and confirmed a locus (
THNSL2
) previously reported to be associated with abdominal fat in women.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26480920</pmid><doi>10.1038/ijo.2015.217</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-4398-8237</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0307-0565 |
| ispartof | International Journal of Obesity, 2016-04, Vol.40 (4), p.662-674 |
| issn | 0307-0565 1476-5497 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4821694 |
| source | MEDLINE; SpringerLink Journals; Nature Journals Online |
| subjects | 45 45/43 59 59/57 631/208 631/208/205/2138 692/499 692/699/2743/393 692/700/139/2818 Abdomen Adipose tissue Adipose tissues Adult Analysis Black or African American - genetics Body fat Body Mass Index Body size Cardiovascular Diseases - etiology Cardiovascular Diseases - genetics Cardiovascular Diseases - physiopathology Chromosome 10 Chromosome 7 Chromosomes Epidemiology Female Genes Genetic Predisposition to Disease - genetics Genome-wide association studies Genome-Wide Association Study Genomes Health Promotion and Disease Prevention Humans Inflammation Internal Medicine Intra-Abdominal Fat - metabolism Loci Male Medicine Medicine & Public Health Metabolic Diseases Middle Aged Nucleotides Obesity original-article Phenotype Polymorphism, Single Nucleotide - genetics Potassium channels Public Health Sex Sex Characteristics Sex Factors Single-nucleotide polymorphism Subcutaneous Fat, Abdominal - metabolism Systematic review United States White People - genetics |
| title | Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T08%3A11%3A09IST&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=Genome-wide%20association%20studies%20suggest%20sex-specific%20loci%20associated%20with%20abdominal%20and%20visceral%20fat&rft.jtitle=International%20Journal%20of%20Obesity&rft.au=Sung,%20Y%20J&rft.date=2016-04-01&rft.volume=40&rft.issue=4&rft.spage=662&rft.epage=674&rft.pages=662-674&rft.issn=0307-0565&rft.eissn=1476-5497&rft_id=info:doi/10.1038/ijo.2015.217&rft_dat=%3Cgale_pubme%3EA451940709%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=1778400849&rft_id=info:pmid/26480920&rft_galeid=A451940709&rfr_iscdi=true |