Obesity susceptibility genetic variants identified from recent genome-wide association studies: implications in a chinese population.
BACKGROUND
Recent large-scale genome-wide association studies identified novel genetic variants associated with obesity and body mass index (BMI) in addition to the well-described FTO and MC4R genetic variants.


OBJECTIVE
This study aimed to examine 13 previously reported obesity and/or BMI-associated loci for associations with obesity in Chinese.


METHODS
This was a cross-sectional case-control study in 470 obese cases (BMI > or =27.5 kg/m(2)) and 700 normal-weight controls (18.5 < or = BMI < or = 23.0 kg/m(2)).


RESULTS
A significant association with obesity could be replicated (one tailed P < 0.05) in seven of the 13 single-nucleotide polymorphisms (SNPs) in the case-control study. These included GNPDA2 rs10938397 (P = 7.3 x 10(-4)); FTO rs8050136 (P = 8 x 10(-4)); MC4R rs17782313 (P = 1.2 x 10(-3)); KCTD15 rs29941 (P = 8 x 10(-3)); SFRS10-ETV5-DGKG rs7647305 (P = 0.023); SEC16B-RASAL2 rs10913469 (P = 0.041); and NEGR1 rs3101336 (P = 0.046). Combined genetic risk scores were calculated, and we observed ORs ranging from 1.17 to 1.23 for each unit increase in the genetic risk scores. Associations with obesity-related quantitative traits were analyzed separately for cases and controls. KCTD15 SNP rs29941 (P = 1 x 10(-3)) was significantly associated with fasting glucose in the control group, whereas only the FTO SNP rs8050136 was associated with BMI (P = 3.5 x 10(-3)) in the obese group. However, in an extension study of 1938 subjects from the population-based Hong Kong Cardiovascular Risk Factors Prevalence Study, rs8050136, rs10938397, and rs17782313 showed significant associations with BMI.


CONCLUSIONS
We have succeeded in replicating, in a Chinese population, the associations with obesity in seven SNPs reported in recent genome-wide association studies. Further functional and fine-mapping studies to elucidate the roles of these putative obesity-related genes and genetic variants are warranted.
Cheung
Chloe Y Y
CY
Department of Medicine, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong.
Tso
Annette W K
AW
Cheung
Bernard M Y
BM
Xu
Aimin
A
Ong
K L
KL
Fong
Carol H Y
CH
Wat
Nelson M S
NM
Janus
Edward D
ED
Sham
Pak C
PC
Lam
Karen S L
KS
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005951:Glucose Tolerance Test; D006723:Hong Kong; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012044:Regression Analysis; D012307:Risk Factors; D055105:Waist Circumference
D001786:Blood Glucose