A tagging SNP in INSIG2 is associated with obesity-related phenotypes among Samoans.
BACKGROUND
A genome wide association study found significant association of a sequence variant, rs7566605, in the insulin-induced gene 2 (INSIG2) with obesity. However, the association remained inconclusive in follow-up studies. We tested for association of four tagging SNPs (tagSNPs) including this variant with body mass index (BMI) and abdominal circumference (ABDCIR) in the Samoans of the Western Pacific, a population with high levels of obesity.


METHODS
We studied 907 adult Samoan participants from a longitudinal study of adiposity and cardiovascular disease risk in two polities, American Samoa and Samoa. Four tagSNPs were identified from the Chinese HapMap database based on pairwise r2 of >or=0.8 and minor allele frequency of >or=0.05. Genotyping was performed using the TaqMan assay. Tests of association with BMI and ABDCIR were performed under the additive model.


RESULTS
We did not find association of rs7566605 with either BMI or ABDCIR in any group of the Samoans. However, the most distally located tagSNPs in Intron 3 of the gene, rs9308762, showed significant association with both BMI (p-value 0.024) and ABDCIR (p-value 0.009) in the combined sample and with BMI (p-value 0.038) in the sample from Samoa.


CONCLUSIONS
Although rs7566605 was not significantly associated with obesity in our study population, we can not rule out the involvement of INSIG2 in obesity related traits as we found significant association of another tagSNP in INSIG2 with both BMI and ABDCIR. This study suggests the importance of comprehensive assessment of sequence variants within a gene in association studies.
Deka
Ranjan
R
Center for Genome Information, Department of Environmental Health, University of Cincinnati College of Medicine, 3223 Eden Avenue, Cincinnati, OH 45267, USA. ranjan.deka@uc.edu
Xu
Ling
L
Pal
Prodipto
P
Toelupe
Palanitina T
PT
Laumoli
Tuiasina S
TS
Xi
Huifeng
H
Zhang
Ge
G
Weeks
Daniel E
DE
McGarvey
Stephen T
ST
D050154:Adiposity / Q000235:genetics; D000328:Adult; D015992:Body Mass Index; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018947:Samoa; D055105:Waist Circumference / Q000235:genetics
C467727:INSIG2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins