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Associations of variants in FTO and Near MC4R with obesity traits in South Asian Indians

Associations of variants in FTO and Near MC4R with obesity traits in South Asian Indians
Associations of variants in FTO and Near MC4R with obesity traits in South Asian Indians
Recent genome-wide association studies show that loci in FTO and melanocortin 4 receptor (MC4R) associate with obesity-related traits. Outside Western populations the associations between these variants have not always been consistent and in Indians it has been suggested that FTO relates to diabetes without an obvious intermediary obesity phenotype. We investigated the association between genetic variants in FTO (rs9939609) and near MC4R (rs17782313) with obesity- and type 2 diabetes (T2DM)-related traits in a longitudinal birth cohort of 2,151 healthy individuals from the Vellore birth cohort in South India. The FTO locus displayed significant associations with several conventional obesity-related anthropometric traits. The per allele increase is about 1% for BMI, waist circumference (WC), hip circumference (HC), and waist—hip ratio. Consistent associations were observed for adipose tissue-specific measurements such as skinfold thickness reinforcing the association with obesity-related traits. Obesity associations for the MC4R locus were weak or nonsignificant but a signal for height (P < 0.001) was observed. The effect on obesity-related traits for FTO was seen in adulthood, but not at younger ages. The loci also showed nominal associations with increased blood glucose but these associations were lost on BMI adjustment. The effect of FTO on obesity-related traits was driven by an urban environmental influence. We conclude that rs9939609 variant in the FTO locus is associated with measures of adiposity and metabolic consequences in South Indians with an enhanced effect associated with urban living. The detection of these associations in Indians is challenging because conventional anthropometric obesity measures work poorly in the Indian “thin-fat” phenotype
1930-7381
2268-2277
Vasan, Senthil K.
57b46c7b-074d-4d99-a284-40b592aec067
Fall, Tove
51914974-a3a4-4a45-b6f9-90e7d0b481cb
Neville, Matthew J.
b7c9383b-0713-4c97-9d84-cb79ebde7949
Antonisamy, Belavendra
ec356bbb-f468-48a3-a375-ec2f3b20852a
Fall, Caroline H.
7171a105-34f5-4131-89d7-1aa639893b18
Geethanjali, Finney S.
a3e2b129-87f5-40de-bcaf-af4f2e76a500
Gu, Harvest F.
6e5e0668-ed1b-4b6a-85f7-707ace915b1c
Ragupathy, P.alany
ef6a84a5-7fe2-4598-9882-9c430ea68655
Samuel, Prasanna
1279c574-c106-407d-8c8d-b93f1e93eead
Thomas, Nihal
c278277e-19ca-43fd-9d42-d9b4d9667001
Brismar, Kerstin
8383770e-65c2-4018-84b1-8dbec21bc0d2
Ingelsson, Erik
3a848725-a6a9-4234-abc5-db91abbf2452
Karpe, Fredrik
05abcb32-83b7-44eb-ab12-7c360f4f9c12
Vasan, Senthil K.
57b46c7b-074d-4d99-a284-40b592aec067
Fall, Tove
51914974-a3a4-4a45-b6f9-90e7d0b481cb
Neville, Matthew J.
b7c9383b-0713-4c97-9d84-cb79ebde7949
Antonisamy, Belavendra
ec356bbb-f468-48a3-a375-ec2f3b20852a
Fall, Caroline H.
7171a105-34f5-4131-89d7-1aa639893b18
Geethanjali, Finney S.
a3e2b129-87f5-40de-bcaf-af4f2e76a500
Gu, Harvest F.
6e5e0668-ed1b-4b6a-85f7-707ace915b1c
Ragupathy, P.alany
ef6a84a5-7fe2-4598-9882-9c430ea68655
Samuel, Prasanna
1279c574-c106-407d-8c8d-b93f1e93eead
Thomas, Nihal
c278277e-19ca-43fd-9d42-d9b4d9667001
Brismar, Kerstin
8383770e-65c2-4018-84b1-8dbec21bc0d2
Ingelsson, Erik
3a848725-a6a9-4234-abc5-db91abbf2452
Karpe, Fredrik
05abcb32-83b7-44eb-ab12-7c360f4f9c12

Vasan, Senthil K., Fall, Tove, Neville, Matthew J., Antonisamy, Belavendra, Fall, Caroline H., Geethanjali, Finney S., Gu, Harvest F., Ragupathy, P.alany, Samuel, Prasanna, Thomas, Nihal, Brismar, Kerstin, Ingelsson, Erik and Karpe, Fredrik (2012) Associations of variants in FTO and Near MC4R with obesity traits in South Asian Indians. Obesity, 20 (11), 2268-2277. (doi:10.1038/oby.2012.64). (PMID:22421923)

Record type: Article

Abstract

Recent genome-wide association studies show that loci in FTO and melanocortin 4 receptor (MC4R) associate with obesity-related traits. Outside Western populations the associations between these variants have not always been consistent and in Indians it has been suggested that FTO relates to diabetes without an obvious intermediary obesity phenotype. We investigated the association between genetic variants in FTO (rs9939609) and near MC4R (rs17782313) with obesity- and type 2 diabetes (T2DM)-related traits in a longitudinal birth cohort of 2,151 healthy individuals from the Vellore birth cohort in South India. The FTO locus displayed significant associations with several conventional obesity-related anthropometric traits. The per allele increase is about 1% for BMI, waist circumference (WC), hip circumference (HC), and waist—hip ratio. Consistent associations were observed for adipose tissue-specific measurements such as skinfold thickness reinforcing the association with obesity-related traits. Obesity associations for the MC4R locus were weak or nonsignificant but a signal for height (P < 0.001) was observed. The effect on obesity-related traits for FTO was seen in adulthood, but not at younger ages. The loci also showed nominal associations with increased blood glucose but these associations were lost on BMI adjustment. The effect of FTO on obesity-related traits was driven by an urban environmental influence. We conclude that rs9939609 variant in the FTO locus is associated with measures of adiposity and metabolic consequences in South Indians with an enhanced effect associated with urban living. The detection of these associations in Indians is challenging because conventional anthropometric obesity measures work poorly in the Indian “thin-fat” phenotype

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Published date: November 2012
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 347101
URI: http://eprints.soton.ac.uk/id/eprint/347101
ISSN: 1930-7381
PURE UUID: 43489292-ec33-43e5-9c96-3b124559cc40
ORCID for Caroline H. Fall: ORCID iD orcid.org/0000-0003-4402-5552

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Date deposited: 17 Jan 2013 11:01
Last modified: 18 Feb 2021 16:37

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Contributors

Author: Senthil K. Vasan
Author: Tove Fall
Author: Matthew J. Neville
Author: Belavendra Antonisamy
Author: Finney S. Geethanjali
Author: Harvest F. Gu
Author: P.alany Ragupathy
Author: Prasanna Samuel
Author: Nihal Thomas
Author: Kerstin Brismar
Author: Erik Ingelsson
Author: Fredrik Karpe

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