Association Study of 25 Type 2 Diabetes Related Loci with Measures of Obesity in Indian Sib Pairs

Vipin Gupta; Donipadi Guru Vinay; Ulla Sovio; Sajjad Rafiq; Madamchetty Venkata Kranthi Kumar; Charles Spurgeon Janipalli; David Evans; Kulathu Radha Mani; Madana Narasimha Sandeep; Amy Taylor; Sanjay Kinra; Ruth Sullivan; Liza Bowen; Nicholas Timpson; George Davey Smith; Frank Dudbridge; Dorairaj Prabhakaran; Yoav Ben-Shlomo; Kolli Srinath Reddy; Shah Ebrahim; Giriraj Ratan Chandak; Indian Migration Study Grp

doi:10.1371/journal.pone.0053944

Association Study of 25 Type 2 Diabetes Related Loci with Measures of Obesity in Indian Sib Pairs

Vipin Gupta^*, Donipadi Guru Vinay, Ulla Sovio, Sajjad Rafiq, Madamchetty Venkata Kranthi Kumar, Charles Spurgeon Janipalli, David Evans, Kulathu Radha Mani, Madana Narasimha Sandeep, Amy Taylor, Sanjay Kinra, Ruth Sullivan, Liza Bowen, Nicholas Timpson, George Davey Smith, Frank Dudbridge, Dorairaj Prabhakaran, Yoav Ben-Shlomo, Kolli Srinath Reddy, Shah EbrahimGiriraj Ratan Chandak, Indian Migration Study Grp

^*Corresponding author for this work

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Abstract

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) (b = 0.13, p = 0.001) and (beta = 0.09, p = 0.002), respectively and weight (beta = 0.13, p = 0.001) and (beta = 0.09, p = 0.001), respectively. CXCR4 variant was also strongly associated with body fat (beta = 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, FLJ3970 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.

Original language	English
Article number	ARTN e53944
Number of pages	6
Journal	PLoS ONE
Volume	8
Issue number	1
DOIs	https://doi.org/10.1371/journal.pone.0053944
Publication status	Published - 17 Jan 2013

Structured keywords

Brain and Behaviour
Tobacco and Alcohol

Keywords

RISK
FTO GENE
GENOME-WIDE ASSOCIATION
METABOLIC TRAITS
GENETIC-VARIANTS
SUSCEPTIBILITY LOCI
LINKAGE
INDIVIDUALS
BODY-MASS INDEX
METAANALYSIS

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Gupta, V., Vinay, D. G., Sovio, U., Rafiq, S., Kumar, M. V. K., Janipalli, C. S., Evans, D., Mani, K. R., Sandeep, M. N., Taylor, A., Kinra, S., Sullivan, R., Bowen, L., Timpson, N., Smith, G. D., Dudbridge, F., Prabhakaran, D., Ben-Shlomo, Y., Reddy, K. S., ... Indian Migration Study Grp (2013). Association Study of 25 Type 2 Diabetes Related Loci with Measures of Obesity in Indian Sib Pairs. PLoS ONE, 8(1), Article ARTN e53944. https://doi.org/10.1371/journal.pone.0053944

@article{435300adc0d04848abb37d5620506faf,

title = "Association Study of 25 Type 2 Diabetes Related Loci with Measures of Obesity in Indian Sib Pairs",

abstract = "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) (b = 0.13, p = 0.001) and (beta = 0.09, p = 0.002), respectively and weight (beta = 0.13, p = 0.001) and (beta = 0.09, p = 0.001), respectively. CXCR4 variant was also strongly associated with body fat (beta = 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, FLJ3970 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.",

keywords = "RISK, FTO GENE, GENOME-WIDE ASSOCIATION, METABOLIC TRAITS, GENETIC-VARIANTS, SUSCEPTIBILITY LOCI, LINKAGE, INDIVIDUALS, BODY-MASS INDEX, METAANALYSIS",

author = "Vipin Gupta and Vinay, {Donipadi Guru} and Ulla Sovio and Sajjad Rafiq and Kumar, {Madamchetty Venkata Kranthi} and Janipalli, {Charles Spurgeon} and David Evans and Mani, {Kulathu Radha} and Sandeep, {Madana Narasimha} and Amy Taylor and Sanjay Kinra and Ruth Sullivan and Liza Bowen and Nicholas Timpson and Smith, {George Davey} and Frank Dudbridge and Dorairaj Prabhakaran and Yoav Ben-Shlomo and Reddy, {Kolli Srinath} and Shah Ebrahim and Chandak, {Giriraj Ratan} and {Indian Migration Study Grp}",

year = "2013",

month = jan,

day = "17",

doi = "10.1371/journal.pone.0053944",

language = "English",

volume = "8",

journal = "PLoS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "1",

}

Gupta, V, Vinay, DG, Sovio, U, Rafiq, S, Kumar, MVK, Janipalli, CS, Evans, D, Mani, KR, Sandeep, MN, Taylor, A, Kinra, S, Sullivan, R, Bowen, L, Timpson, N , Smith, GD, Dudbridge, F, Prabhakaran, D, Ben-Shlomo, Y, Reddy, KS, Ebrahim, S, Chandak, GR & Indian Migration Study Grp 2013, 'Association Study of 25 Type 2 Diabetes Related Loci with Measures of Obesity in Indian Sib Pairs', PLoS ONE, vol. 8, no. 1, ARTN e53944. https://doi.org/10.1371/journal.pone.0053944

TY - JOUR

T1 - Association Study of 25 Type 2 Diabetes Related Loci with Measures of Obesity in Indian Sib Pairs

AU - Gupta, Vipin

AU - Vinay, Donipadi Guru

AU - Sovio, Ulla

AU - Rafiq, Sajjad

AU - Kumar, Madamchetty Venkata Kranthi

AU - Janipalli, Charles Spurgeon

AU - Evans, David

AU - Mani, Kulathu Radha

AU - Sandeep, Madana Narasimha

AU - Taylor, Amy

AU - Kinra, Sanjay

AU - Sullivan, Ruth

AU - Bowen, Liza

AU - Timpson, Nicholas

AU - Smith, George Davey

AU - Dudbridge, Frank

AU - Prabhakaran, Dorairaj

AU - Ben-Shlomo, Yoav

AU - Reddy, Kolli Srinath

AU - Ebrahim, Shah

AU - Chandak, Giriraj Ratan

AU - Indian Migration Study Grp

PY - 2013/1/17

Y1 - 2013/1/17

N2 - 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) (b = 0.13, p = 0.001) and (beta = 0.09, p = 0.002), respectively and weight (beta = 0.13, p = 0.001) and (beta = 0.09, p = 0.001), respectively. CXCR4 variant was also strongly associated with body fat (beta = 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, FLJ3970 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.

AB - 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) (b = 0.13, p = 0.001) and (beta = 0.09, p = 0.002), respectively and weight (beta = 0.13, p = 0.001) and (beta = 0.09, p = 0.001), respectively. CXCR4 variant was also strongly associated with body fat (beta = 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, FLJ3970 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.

KW - RISK

KW - FTO GENE

KW - GENOME-WIDE ASSOCIATION

KW - METABOLIC TRAITS

KW - GENETIC-VARIANTS

KW - SUSCEPTIBILITY LOCI

KW - LINKAGE

KW - INDIVIDUALS

KW - BODY-MASS INDEX

KW - METAANALYSIS

U2 - 10.1371/journal.pone.0053944

DO - 10.1371/journal.pone.0053944

M3 - Article (Academic Journal)

C2 - 23349771

SN - 1932-6203

VL - 8

JO - PLoS ONE

JF - PLoS ONE

IS - 1

M1 - ARTN e53944

ER -

Association Study of 25 Type 2 Diabetes Related Loci with Measures of Obesity in Indian Sib Pairs

Abstract

Structured keywords

Keywords

UN SDGs

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