Low-frequency variants in HMGA1 are not associated with type 2 diabetes risk

Soumya Raychaudhuri; Marcel Marquez; Marlène Huyvaert; John R B Perry; Richard D. Pearson; Mario Falchi; Andrew P. Morris; Sidonie Vivequin; Stéphane Lobbens; Loïc Yengo; Stefan Gaget; Francois Pattou; Odile Poulain-Godefroy; Guillaume Charpentier; Lena M S Carlsson; Peter Jacobson; Lars Sjöström; Olivier Lantieri; Barbara Heude; Andrew Walley; Beverley Balkau; Michel Marre; Philippe Froguel; Stéphane Cauchi

doi:10.2337/db11-0728

Low-frequency variants in HMGA1 are not associated with type 2 diabetes risk

Soumya Raychaudhuri, Marcel Marquez, Marlène Huyvaert, John R B Perry, Richard D. Pearson, Mario Falchi, Andrew P. Morris, Sidonie Vivequin, Stéphane Lobbens, Loïc Yengo, Stefan Gaget, Francois Pattou, Odile Poulain-Godefroy, Guillaume Charpentier, Lena M S Carlsson, Peter Jacobson, Lars Sjöström, Olivier Lantieri, Barbara Heude, Andrew WalleyBeverley Balkau, Michel Marre, Philippe Froguel, Stéphane Cauchi

Research output: Contribution to journal › Article › peer-review

Abstract

It has recently been suggested that the low-frequency c.136-14-136-13insC variant in high-mobility group A1 (HMGA1) may strongly contribute to insulin resistance and type 2 diabetes risk. In our study, we attempted to confirm that HMGA1 is a novel type 2 diabetes locus in French Caucasians. The gene was sequenced in 368 type 2 diabetic case subjects with a family history of type 2 diabetes and 372 normoglycemic control subjects without a family history of type 2 diabetes. None of the 41 genetic variations identified were associated with type 2 diabetes. The lack of association between the c.136-14-136-13insC variant and type 2 diabetes was confirmed in an independent French group of 4,538 case subjects and 4,015 control subjects and in a large meta-analysis of 16,605 case subjects and 46,179 control subjects. Finally, this variant had no effects on metabolic traits and was not involved in variations of HMGA1 and insulin receptor (INSR) expressions. The c.136-14-136-13insC variant was not associated with type 2 diabetes in individuals of European descent. Our study emphasizes the need to analyze a large number of subjects to reliably assess the association of low-frequency variants with the disease. © 2012 by the American Diabetes Association.

Original language	English
Pages (from-to)	524-530
Number of pages	6
Journal	Diabetes
Volume	61
Issue number	2
DOIs	https://doi.org/10.2337/db11-0728
Publication status	Published - Feb 2012

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10.2337/db11-0728

http://diabetes.diabetesjournals.org/content/61/2/524.full.pdf+html

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Raychaudhuri, S., Marquez, M., Huyvaert, M., Perry, J. R. B., Pearson, R. D., Falchi, M., Morris, A. P., Vivequin, S., Lobbens, S., Yengo, L., Gaget, S., Pattou, F., Poulain-Godefroy, O., Charpentier, G., Carlsson, L. M. S., Jacobson, P., Sjöström, L., Lantieri, O., Heude, B., ... Cauchi, S. (2012). Low-frequency variants in HMGA1 are not associated with type 2 diabetes risk. Diabetes, 61(2), 524-530. https://doi.org/10.2337/db11-0728

@article{a1faa1444a9048c2b6c5eebc0a6ea100,

title = "Low-frequency variants in HMGA1 are not associated with type 2 diabetes risk",

abstract = "It has recently been suggested that the low-frequency c.136-14-136-13insC variant in high-mobility group A1 (HMGA1) may strongly contribute to insulin resistance and type 2 diabetes risk. In our study, we attempted to confirm that HMGA1 is a novel type 2 diabetes locus in French Caucasians. The gene was sequenced in 368 type 2 diabetic case subjects with a family history of type 2 diabetes and 372 normoglycemic control subjects without a family history of type 2 diabetes. None of the 41 genetic variations identified were associated with type 2 diabetes. The lack of association between the c.136-14-136-13insC variant and type 2 diabetes was confirmed in an independent French group of 4,538 case subjects and 4,015 control subjects and in a large meta-analysis of 16,605 case subjects and 46,179 control subjects. Finally, this variant had no effects on metabolic traits and was not involved in variations of HMGA1 and insulin receptor (INSR) expressions. The c.136-14-136-13insC variant was not associated with type 2 diabetes in individuals of European descent. Our study emphasizes the need to analyze a large number of subjects to reliably assess the association of low-frequency variants with the disease. {\textcopyright} 2012 by the American Diabetes Association.",

author = "Soumya Raychaudhuri and Marcel Marquez and Marl{\`e}ne Huyvaert and Perry, {John R B} and Pearson, {Richard D.} and Mario Falchi and Morris, {Andrew P.} and Sidonie Vivequin and St{\'e}phane Lobbens and Lo{\"i}c Yengo and Stefan Gaget and Francois Pattou and Odile Poulain-Godefroy and Guillaume Charpentier and Carlsson, {Lena M S} and Peter Jacobson and Lars Sj{\"o}str{\"o}m and Olivier Lantieri and Barbara Heude and Andrew Walley and Beverley Balkau and Michel Marre and Philippe Froguel and St{\'e}phane Cauchi",

note = "064890, Wellcome Trust, United Kingdom081682, Wellcome Trust, United Kingdom",

year = "2012",

month = feb,

doi = "10.2337/db11-0728",

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Raychaudhuri, S, Marquez, M, Huyvaert, M, Perry, JRB, Pearson, RD, Falchi, M, Morris, AP, Vivequin, S, Lobbens, S, Yengo, L, Gaget, S, Pattou, F, Poulain-Godefroy, O, Charpentier, G, Carlsson, LMS, Jacobson, P, Sjöström, L, Lantieri, O, Heude, B, Walley, A, Balkau, B, Marre, M, Froguel, P & Cauchi, S 2012, 'Low-frequency variants in HMGA1 are not associated with type 2 diabetes risk', Diabetes, vol. 61, no. 2, pp. 524-530. https://doi.org/10.2337/db11-0728

TY - JOUR

T1 - Low-frequency variants in HMGA1 are not associated with type 2 diabetes risk

AU - Raychaudhuri, Soumya

AU - Marquez, Marcel

AU - Huyvaert, Marlène

AU - Perry, John R B

AU - Pearson, Richard D.

AU - Falchi, Mario

AU - Morris, Andrew P.

AU - Vivequin, Sidonie

AU - Lobbens, Stéphane

AU - Yengo, Loïc

AU - Gaget, Stefan

AU - Pattou, Francois

AU - Poulain-Godefroy, Odile

AU - Charpentier, Guillaume

AU - Carlsson, Lena M S

AU - Jacobson, Peter

AU - Sjöström, Lars

AU - Lantieri, Olivier

AU - Heude, Barbara

AU - Walley, Andrew

AU - Balkau, Beverley

AU - Marre, Michel

AU - Froguel, Philippe

AU - Cauchi, Stéphane

N1 - 064890, Wellcome Trust, United Kingdom081682, Wellcome Trust, United Kingdom

PY - 2012/2

Y1 - 2012/2

N2 - It has recently been suggested that the low-frequency c.136-14-136-13insC variant in high-mobility group A1 (HMGA1) may strongly contribute to insulin resistance and type 2 diabetes risk. In our study, we attempted to confirm that HMGA1 is a novel type 2 diabetes locus in French Caucasians. The gene was sequenced in 368 type 2 diabetic case subjects with a family history of type 2 diabetes and 372 normoglycemic control subjects without a family history of type 2 diabetes. None of the 41 genetic variations identified were associated with type 2 diabetes. The lack of association between the c.136-14-136-13insC variant and type 2 diabetes was confirmed in an independent French group of 4,538 case subjects and 4,015 control subjects and in a large meta-analysis of 16,605 case subjects and 46,179 control subjects. Finally, this variant had no effects on metabolic traits and was not involved in variations of HMGA1 and insulin receptor (INSR) expressions. The c.136-14-136-13insC variant was not associated with type 2 diabetes in individuals of European descent. Our study emphasizes the need to analyze a large number of subjects to reliably assess the association of low-frequency variants with the disease. © 2012 by the American Diabetes Association.

AB - It has recently been suggested that the low-frequency c.136-14-136-13insC variant in high-mobility group A1 (HMGA1) may strongly contribute to insulin resistance and type 2 diabetes risk. In our study, we attempted to confirm that HMGA1 is a novel type 2 diabetes locus in French Caucasians. The gene was sequenced in 368 type 2 diabetic case subjects with a family history of type 2 diabetes and 372 normoglycemic control subjects without a family history of type 2 diabetes. None of the 41 genetic variations identified were associated with type 2 diabetes. The lack of association between the c.136-14-136-13insC variant and type 2 diabetes was confirmed in an independent French group of 4,538 case subjects and 4,015 control subjects and in a large meta-analysis of 16,605 case subjects and 46,179 control subjects. Finally, this variant had no effects on metabolic traits and was not involved in variations of HMGA1 and insulin receptor (INSR) expressions. The c.136-14-136-13insC variant was not associated with type 2 diabetes in individuals of European descent. Our study emphasizes the need to analyze a large number of subjects to reliably assess the association of low-frequency variants with the disease. © 2012 by the American Diabetes Association.

U2 - 10.2337/db11-0728

DO - 10.2337/db11-0728

M3 - Article

C2 - 22210315

SN - 0012-1797

SN - 1939-327X

VL - 61

SP - 524

EP - 530

JO - Diabetes

JF - Diabetes

IS - 2

ER -

Low-frequency variants in HMGA1 are not associated with type 2 diabetes risk

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