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

doi:10.1038/ijo.2015.217

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 journal › Article › peer-review

76 Scopus citations

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.

Original language	English
Pages (from-to)	662-674
Number of pages	13
Journal	International Journal of Obesity
Volume	40
Issue number	4
DOIs	https://doi.org/10.1038/ijo.2015.217
State	Published - Apr 1 2016

Access to Document

10.1038/ijo.2015.217

Cite this

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. (2016). Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat. International Journal of Obesity, 40(4), 662-674. https://doi.org/10.1038/ijo.2015.217

@article{701775612df64e4198bb2e1589c59fd4,

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<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.",

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",

note = "Publisher Copyright: {\textcopyright} 2016 Macmillan Publishers Limited.",

year = "2016",

month = apr,

day = "1",

doi = "10.1038/ijo.2015.217",

language = "English",

volume = "40",

pages = "662--674",

journal = "International Journal of Obesity",

issn = "0307-0565",

number = "4",

}

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 2016, 'Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat', International Journal of Obesity, vol. 40, no. 4, pp. 662-674. https://doi.org/10.1038/ijo.2015.217

TY - JOUR

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 - 2016/4/1

Y1 - 2016/4/1

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<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.

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<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.

UR - http://www.scopus.com/inward/record.url?scp=84947998279&partnerID=8YFLogxK

U2 - 10.1038/ijo.2015.217

DO - 10.1038/ijo.2015.217

M3 - Article

C2 - 26480920

AN - SCOPUS:84947998279

SN - 0307-0565

VL - 40

SP - 662

EP - 674

JO - International Journal of Obesity

JF - International Journal of Obesity

IS - 4

ER -

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

Abstract

Access to Document

Other files and links

Fingerprint

Cite this