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 tissue ratio (VSR).


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.
Division of Biostatistics, Washington University School of Medicine, St Louis, MO, USA.
Y J
YJ
Sung
Department of Kinesiology, School of Medicine and Institute of Nutrition and Functional Foods, Laval University, Québec, Canada.
L
L
Pérusse
Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
M A
MA
Sarzynski
Department of Epidemiology, Human Genetics and Environmental Sciences, Center for Human Genetics, University of Texas Health Science Center, Houston, TX, USA.
M
M
Fornage
Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
S
S
Sidney
Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
B
B
Sternfeld
Division of Biostatistics, Washington University School of Medicine, St Louis, MO, USA.
T
T
Rice
Department of Radiology, School of Medicine, Vanderbilt University, Nahsville, TN, USA.
J G
JG
Terry
Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
D R
DR
Jacobs
Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
P
P
Katzmarzyk
South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville, TX, USA.
J E
JE
Curran
Department of Radiology, School of Medicine, Vanderbilt University, Nahsville, TN, USA.
J
http://orcid.org/0000-0002-4398-8237
J
Jeffrey Carr
South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville, TX, USA.
J
J
Blangero
Cardiovascular and Metabolic Disorders Program and Center for Computational Biology, Duke-NUS Graduate Medical School, Singapore.
S
S
Ghosh
Department of Kinesiology, School of Medicine and Institute of Nutrition and Functional Foods, Laval University, Québec, Canada.|Centre de recherché de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, Canada.
J-P
JP
Després
Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
T
T
Rankinen
Division of Biostatistics, Washington University School of Medicine, St Louis, MO, USA.
D C
DC
Rao
Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
C
C
Bouchard
D000328:Adult; D001741:Black or African American / Q000235:genetics; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012727:Sex Characteristics; D012737:Sex Factors; D050507:Subcutaneous Fat, Abdominal / Q000378:metabolism*; D014481:United States; D044465:White People / Q000235:genetics