Association study of 25 type 2 diabetes related Loci with measures of obesity in Indian sib pairs.
Obesity is an established risk factor for type 2 diabetes (T2D) and they are metabolically related through the mechanism of insulin resistance. In order to explore how common genetic variants associated with T2D correlate with body mass index (BMI), we examined the influence of 25 T2D associated loci on obesity risk. We used 5056 individuals (2528 sib-pairs) recruited in Indian Migration Study and conducted within sib-pair analysis for six obesity phenotypes. We found associations of variants in CXCR4 (rs932206) and HHEX (rs5015480) with higher body mass index (BMI) (β=0.13, p=0.001) and (β=0.09, p=0.002), respectively and weight (β=0.13, p=0.001) and (β=0.09, p=0.001), respectively. CXCR4 variant was also strongly associated with body fat (β=0.10, p=0.0004). In addition, we demonstrated associations of CXCR4 and HHEX with overweight/obesity (OR=1.6, p=0.003) and (OR=1.4, p=0.002), respectively, in 1333 sib-pairs (2666 individuals). We observed marginal evidence of associations between variants at six loci (TCF7L2, NGN3, FOXA2, LOC646279, FLJ39370 and THADA) and waist hip ratio (WHR), BMI and/or overweight which needs to be validated in larger set of samples. All the above findings were independent of daily energy consumption and physical activity level. The risk score estimates based on eight significant loci (including nominal associations) showed associations with WHR and body fat which were independent of BMI. In summary, we establish the role of T2D associated loci in influencing the measures of obesity in Indian population, suggesting common underlying pathophysiology across populations.
South Asia Network for Chronic Disease, Public Health Foundation of India, New Delhi, India. udaiig@gmail.com
Vipin
V
Gupta
Donipadi Guru
DG
Vinay
Ulla
U
Sovio
Sajjad
S
Rafiq
Madamchetty Venkata
MV
Kranthi Kumar
Charles Spurgeon
CS
Janipalli
David
D
Evans
Kulathu Radha
KR
Mani
Madana Narasimha
MN
Sandeep
Amy
A
Taylor
Sanjay
S
Kinra
Ruth
R
Sullivan
Liza
L
Bowen
Nicholas
N
Timpson
George Davey
GD
Smith
Frank
F
Dudbridge
Dorairaj
D
Prabhakaran
Yoav
Y
Ben-Shlomo
Kolli Srinath
KS
Reddy
Shah
S
Ebrahim
Giriraj Ratan
GR
Chandak
D000328:Adult; D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D051542:Hepatocyte Nuclear Factor 3-beta / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007194:India; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D009765:Obesity / Q000150:complications / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D019718:Receptors, CXCR4 / Q000235:genetics; D035781:Siblings; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014171:Transients and Migrants / Q000706:statistics & numerical data; D049629:Waist-Hip Ratio
D051792:Basic Helix-Loop-Helix Proteins; D051542:Hepatocyte Nuclear Factor 3-beta; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D019718:Receptors, CXCR4; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; C527276:CXCR4 protein, human; C496502:FOXA2 protein, human; C078492:HHEX protein, human; C498695:NEUROG3 protein, human; C544894:TCF7L2 protein, human; C477698:THADA protein, human