Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat

Y. J. Sung, L. Pérusse, M. A. Sarzynski, M. Fornage, S. Sidney, B. Sternfeld, T. Rice, J. G. Terry, D. R. Jacobs, P. Katzmarzyk, J. E. Curran, J. Jeffrey Carr, J. Blangero, S. Ghosh, J. P. Després, T. Rankinen, D. C. Rao, C. Bouchard

    Research output: Contribution to journalArticle

    31 Citations (Scopus)

    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-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-8) locus for SAT in women with 11 SNPs encompassing the MLLT10, DNAJC1 and EBLN1 genes on chromosome 10p12.31 (P=3.97 × 108 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.International Journal of Obesity advance online publication, 24 November 2015; doi:10.1038/ijo.2015.217.

    Original languageEnglish (US)
    JournalInternational Journal of Obesity
    DOIs
    StateAccepted/In press - Oct 20 2015

    Fingerprint

    Intra-Abdominal Fat
    Genome-Wide Association Study
    Abdominal Fat
    Single Nucleotide Polymorphism
    Subcutaneous Fat
    Body Mass Index
    Obesity
    Genes
    Chromosomes
    Inflammation
    African Americans
    Publications
    Meta-Analysis
    Software
    Fats
    Genome

    ASJC Scopus subject areas

    • Medicine (miscellaneous)
    • Nutrition and Dietetics
    • Endocrinology, Diabetes and Metabolism

    Cite this

    Sung, Y. J., Pérusse, L., Sarzynski, M. A., Fornage, M., Sidney, S., Sternfeld, B., ... Bouchard, C. (Accepted/In press). Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat. International Journal of Obesity. https://doi.org/10.1038/ijo.2015.217

    Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat. / 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.

    In: International Journal of Obesity, 20.10.2015.

    Research output: Contribution to journalArticle

    Sung, YJ, Pérusse, L, Sarzynski, MA, Fornage, M, Sidney, S, Sternfeld, B, Rice, T, Terry, JG, Jacobs, DR, Katzmarzyk, P, Curran, JE, Jeffrey Carr, J, Blangero, J, Ghosh, S, Després, JP, Rankinen, T, Rao, DC & Bouchard, C 2015, 'Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat', International Journal of Obesity. https://doi.org/10.1038/ijo.2015.217
    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. / Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat. In: International Journal of Obesity. 2015.
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    title = "Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat",
    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-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-8) locus for SAT in women with 11 SNPs encompassing the MLLT10, DNAJC1 and EBLN1 genes on chromosome 10p12.31 (P=3.97 × 108 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.International Journal of Obesity advance online publication, 24 November 2015; doi:10.1038/ijo.2015.217.",
    author = "Sung, {Y. J.} and L. P{\'e}russe and Sarzynski, {M. A.} and M. Fornage and S. Sidney and B. Sternfeld and T. Rice and Terry, {J. G.} and Jacobs, {D. R.} and P. Katzmarzyk and Curran, {J. E.} and {Jeffrey Carr}, J. and J. Blangero and S. Ghosh and Despr{\'e}s, {J. P.} and T. Rankinen and Rao, {D. C.} and C. Bouchard",
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    day = "20",
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    language = "English (US)",
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    T1 - Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat

    AU - Sung, Y. J.

    AU - Pérusse, L.

    AU - Sarzynski, M. A.

    AU - Fornage, M.

    AU - Sidney, S.

    AU - Sternfeld, B.

    AU - Rice, T.

    AU - Terry, J. G.

    AU - Jacobs, D. R.

    AU - Katzmarzyk, P.

    AU - Curran, J. E.

    AU - Jeffrey Carr, J.

    AU - Blangero, J.

    AU - Ghosh, S.

    AU - Després, J. P.

    AU - Rankinen, T.

    AU - Rao, D. C.

    AU - Bouchard, C.

    PY - 2015/10/20

    Y1 - 2015/10/20

    N2 - 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-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-8) locus for SAT in women with 11 SNPs encompassing the MLLT10, DNAJC1 and EBLN1 genes on chromosome 10p12.31 (P=3.97 × 108 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.International Journal of Obesity advance online publication, 24 November 2015; doi:10.1038/ijo.2015.217.

    AB - 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-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-8) locus for SAT in women with 11 SNPs encompassing the MLLT10, DNAJC1 and EBLN1 genes on chromosome 10p12.31 (P=3.97 × 108 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.International Journal of Obesity advance online publication, 24 November 2015; doi:10.1038/ijo.2015.217.

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