Association analysis of 29,956 individuals confirms that a low-frequency variant at CCND2 halves the risk of type 2 diabetes by enhancing insulin secretion

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Standard

Association analysis of 29,956 individuals confirms that a low-frequency variant at CCND2 halves the risk of type 2 diabetes by enhancing insulin secretion. / Yaghootkar, Hanieh; Stancáková, Alena; Freathy, Rachel M; Vangipurapu, Jagadish; Weedon, Michael N; Xie, Weijia; Wood, Andrew R; Ferrannini, Ele; Mari, Andrea; Ring, Susan M; Lawlor, Debbie A; Davey Smith, George; Jørgensen, Torben; Hansen, Torben; Pedersen, Oluf; Steinthorsdottir, Valgerdur; Guðbjartsson, Daniel F; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Stefansson, Kari; Hattersley, Andrew T; Walker, Mark; Morris, Andrew D; McCarthy, Mark I; Palmer, Colin N A; Laakso, Markku; Frayling, Timothy M.

In: Diabetes, Vol. 64, No. 6, 06.2015, p. 2279-85.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Yaghootkar, H, Stancáková, A, Freathy, RM, Vangipurapu, J, Weedon, MN, Xie, W, Wood, AR, Ferrannini, E, Mari, A, Ring, SM, Lawlor, DA, Davey Smith, G, Jørgensen, T, Hansen, T, Pedersen, O, Steinthorsdottir, V, Guðbjartsson, DF, Thorleifsson, G, Thorsteinsdottir, U, Stefansson, K, Hattersley, AT, Walker, M, Morris, AD, McCarthy, MI, Palmer, CNA, Laakso, M & Frayling, TM 2015, 'Association analysis of 29,956 individuals confirms that a low-frequency variant at CCND2 halves the risk of type 2 diabetes by enhancing insulin secretion', Diabetes, vol. 64, no. 6, pp. 2279-85. https://doi.org/10.2337/db14-1456

APA

Yaghootkar, H., Stancáková, A., Freathy, R. M., Vangipurapu, J., Weedon, M. N., Xie, W., Wood, A. R., Ferrannini, E., Mari, A., Ring, S. M., Lawlor, D. A., Davey Smith, G., Jørgensen, T., Hansen, T., Pedersen, O., Steinthorsdottir, V., Guðbjartsson, D. F., Thorleifsson, G., Thorsteinsdottir, U., ... Frayling, T. M. (2015). Association analysis of 29,956 individuals confirms that a low-frequency variant at CCND2 halves the risk of type 2 diabetes by enhancing insulin secretion. Diabetes, 64(6), 2279-85. https://doi.org/10.2337/db14-1456

Vancouver

Yaghootkar H, Stancáková A, Freathy RM, Vangipurapu J, Weedon MN, Xie W et al. Association analysis of 29,956 individuals confirms that a low-frequency variant at CCND2 halves the risk of type 2 diabetes by enhancing insulin secretion. Diabetes. 2015 Jun;64(6):2279-85. https://doi.org/10.2337/db14-1456

Author

Yaghootkar, Hanieh ; Stancáková, Alena ; Freathy, Rachel M ; Vangipurapu, Jagadish ; Weedon, Michael N ; Xie, Weijia ; Wood, Andrew R ; Ferrannini, Ele ; Mari, Andrea ; Ring, Susan M ; Lawlor, Debbie A ; Davey Smith, George ; Jørgensen, Torben ; Hansen, Torben ; Pedersen, Oluf ; Steinthorsdottir, Valgerdur ; Guðbjartsson, Daniel F ; Thorleifsson, Gudmar ; Thorsteinsdottir, Unnur ; Stefansson, Kari ; Hattersley, Andrew T ; Walker, Mark ; Morris, Andrew D ; McCarthy, Mark I ; Palmer, Colin N A ; Laakso, Markku ; Frayling, Timothy M. / Association analysis of 29,956 individuals confirms that a low-frequency variant at CCND2 halves the risk of type 2 diabetes by enhancing insulin secretion. In: Diabetes. 2015 ; Vol. 64, No. 6. pp. 2279-85.

Bibtex

@article{4c66005535174f70a89333b0ad0ccc8d,
title = "Association analysis of 29,956 individuals confirms that a low-frequency variant at CCND2 halves the risk of type 2 diabetes by enhancing insulin secretion",
abstract = "A recent study identified a low-frequency variant at CCND2 associated with lower risk of type 2 diabetes, enhanced insulin response to a glucose challenge, higher height, and, paradoxically, higher BMI. We aimed to replicate the strength and effect size of these associations in independent samples and to assess the underlying mechanism. We genotyped the variant in 29,956 individuals and tested its association with type 2 diabetes and related traits. The low-frequency allele was associated with a lower risk of type 2 diabetes (OR 0.53; P = 2 × 10−13; 6,647 case vs. 12,645 control subjects), higher disposition index (β = 0.07 log10; P = 2 × 10−11; n = 13,028), and higher Matsuda index of insulin sensitivity (β = 0.02 log10; P = 5 × 10−3; n = 13,118) but not fasting proinsulin (β = 0.01 log10; P = 0.5; n = 6,985). The low frequency allele was associated with higher adult height (β = 1.38 cm; P = 6 × 10−9; n = 13,927), but the association of the variant with BMI (β = 0.36 kg/m2; P = 0.02; n = 24,807), estimated in four population-based samples, was less than in the original publication where the effect estimate was biased by analyzing case subjects with type 2 diabetes and control subjects without diabetes separately. Our study establishes that a low-frequency allele in CCND2 halves the risk of type 2 diabetes primarily through enhanced insulin secretion.",
keywords = "Alleles, Body Mass Index, Cyclin D2, Diabetes Mellitus, Type 2, Gene Frequency, Genotype, Humans, Insulin",
author = "Hanieh Yaghootkar and Alena Stanc{\'a}kov{\'a} and Freathy, {Rachel M} and Jagadish Vangipurapu and Weedon, {Michael N} and Weijia Xie and Wood, {Andrew R} and Ele Ferrannini and Andrea Mari and Ring, {Susan M} and Lawlor, {Debbie A} and {Davey Smith}, George and Torben J{\o}rgensen and Torben Hansen and Oluf Pedersen and Valgerdur Steinthorsdottir and Gu{\dh}bjartsson, {Daniel F} and Gudmar Thorleifsson and Unnur Thorsteinsdottir and Kari Stefansson and Hattersley, {Andrew T} and Mark Walker and Morris, {Andrew D} and McCarthy, {Mark I} and Palmer, {Colin N A} and Markku Laakso and Frayling, {Timothy M}",
note = "{\textcopyright} 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.",
year = "2015",
month = jun,
doi = "10.2337/db14-1456",
language = "English",
volume = "64",
pages = "2279--85",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "6",

}

RIS

TY - JOUR

T1 - Association analysis of 29,956 individuals confirms that a low-frequency variant at CCND2 halves the risk of type 2 diabetes by enhancing insulin secretion

AU - Yaghootkar, Hanieh

AU - Stancáková, Alena

AU - Freathy, Rachel M

AU - Vangipurapu, Jagadish

AU - Weedon, Michael N

AU - Xie, Weijia

AU - Wood, Andrew R

AU - Ferrannini, Ele

AU - Mari, Andrea

AU - Ring, Susan M

AU - Lawlor, Debbie A

AU - Davey Smith, George

AU - Jørgensen, Torben

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - Steinthorsdottir, Valgerdur

AU - Guðbjartsson, Daniel F

AU - Thorleifsson, Gudmar

AU - Thorsteinsdottir, Unnur

AU - Stefansson, Kari

AU - Hattersley, Andrew T

AU - Walker, Mark

AU - Morris, Andrew D

AU - McCarthy, Mark I

AU - Palmer, Colin N A

AU - Laakso, Markku

AU - Frayling, Timothy M

N1 - © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

PY - 2015/6

Y1 - 2015/6

N2 - A recent study identified a low-frequency variant at CCND2 associated with lower risk of type 2 diabetes, enhanced insulin response to a glucose challenge, higher height, and, paradoxically, higher BMI. We aimed to replicate the strength and effect size of these associations in independent samples and to assess the underlying mechanism. We genotyped the variant in 29,956 individuals and tested its association with type 2 diabetes and related traits. The low-frequency allele was associated with a lower risk of type 2 diabetes (OR 0.53; P = 2 × 10−13; 6,647 case vs. 12,645 control subjects), higher disposition index (β = 0.07 log10; P = 2 × 10−11; n = 13,028), and higher Matsuda index of insulin sensitivity (β = 0.02 log10; P = 5 × 10−3; n = 13,118) but not fasting proinsulin (β = 0.01 log10; P = 0.5; n = 6,985). The low frequency allele was associated with higher adult height (β = 1.38 cm; P = 6 × 10−9; n = 13,927), but the association of the variant with BMI (β = 0.36 kg/m2; P = 0.02; n = 24,807), estimated in four population-based samples, was less than in the original publication where the effect estimate was biased by analyzing case subjects with type 2 diabetes and control subjects without diabetes separately. Our study establishes that a low-frequency allele in CCND2 halves the risk of type 2 diabetes primarily through enhanced insulin secretion.

AB - A recent study identified a low-frequency variant at CCND2 associated with lower risk of type 2 diabetes, enhanced insulin response to a glucose challenge, higher height, and, paradoxically, higher BMI. We aimed to replicate the strength and effect size of these associations in independent samples and to assess the underlying mechanism. We genotyped the variant in 29,956 individuals and tested its association with type 2 diabetes and related traits. The low-frequency allele was associated with a lower risk of type 2 diabetes (OR 0.53; P = 2 × 10−13; 6,647 case vs. 12,645 control subjects), higher disposition index (β = 0.07 log10; P = 2 × 10−11; n = 13,028), and higher Matsuda index of insulin sensitivity (β = 0.02 log10; P = 5 × 10−3; n = 13,118) but not fasting proinsulin (β = 0.01 log10; P = 0.5; n = 6,985). The low frequency allele was associated with higher adult height (β = 1.38 cm; P = 6 × 10−9; n = 13,927), but the association of the variant with BMI (β = 0.36 kg/m2; P = 0.02; n = 24,807), estimated in four population-based samples, was less than in the original publication where the effect estimate was biased by analyzing case subjects with type 2 diabetes and control subjects without diabetes separately. Our study establishes that a low-frequency allele in CCND2 halves the risk of type 2 diabetes primarily through enhanced insulin secretion.

KW - Alleles

KW - Body Mass Index

KW - Cyclin D2

KW - Diabetes Mellitus, Type 2

KW - Gene Frequency

KW - Genotype

KW - Humans

KW - Insulin

U2 - 10.2337/db14-1456

DO - 10.2337/db14-1456

M3 - Journal article

C2 - 25605810

VL - 64

SP - 2279

EP - 2285

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 6

ER -

ID: 150711521