Pancreatic beta-cell function and type 2 diabetes risk

Quantify the causal effect using a Mendelian randomization approach based on meta-analyses

Yiqing Song, Edwina Yeung, Aiyi Liu, Tyler J. Vanderweele, Liwei Chen, Chen Lu, Chunling Liu, Enrique F. Schisterman, Yi Ning, Cuilin Zhang

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The objective of the study is to quantify the causal effect of β-cell function on type 2 diabetes by minimizing residual confounding and reverse causation. We employed a Mendelian randomization (MR) approach using TCF7L2 variant rs7903146 as an instrument for lifelong levels of β-cell function. We first conducted two sets of meta-analyses to quantify the association of the TCF7L2 variant with the risk of type 2 diabetes among 55 436 cases and 106 020 controls from 66 studies by calculating pooled odds ratio (OR) and to quantify the associations with multiple direct or indirect measures of β-cell function among 35 052 non-diabetic individuals from 31 studies by calculating pooled mean difference. We further applied the method of MR to obtain the causal estimates for the effect of β-cell function on type 2 diabetes risk based on findings from the meta-analyses. The OR [95% confidence interval (CI)] was 0.87 (0.81-0.93) for each five unit increment in homeostasis model assessment of insulin secretion (HOMA-%B) (P = 3.0 × 10-5). In addition, for measures based on intravenous glucose tolerance test, ORs (95% CI) associated with type 2 diabetes risk were 0.24 (0.08-0.74) (P = 0.01) and 0.14 (0.04-0.48) (P = 0.002) for per 1 standard deviation increment in insulin sensitivity index and disposition index, respectively. Findings from the present study lend support to a causal role of pancreatic β-cell function itself in the etiology of type 2 diabetes.

Original languageEnglish (US)
Article numberdds339
Pages (from-to)5010-5018
Number of pages9
JournalHuman Molecular Genetics
Volume21
Issue number22
DOIs
StatePublished - Nov 1 2012
Externally publishedYes

Fingerprint

Insulin-Secreting Cells
Random Allocation
Type 2 Diabetes Mellitus
Meta-Analysis
Odds Ratio
Confidence Intervals
Glucose Tolerance Test
Causality
Insulin Resistance
Homeostasis
Insulin

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Pancreatic beta-cell function and type 2 diabetes risk : Quantify the causal effect using a Mendelian randomization approach based on meta-analyses. / Song, Yiqing; Yeung, Edwina; Liu, Aiyi; Vanderweele, Tyler J.; Chen, Liwei; Lu, Chen; Liu, Chunling; Schisterman, Enrique F.; Ning, Yi; Zhang, Cuilin.

In: Human Molecular Genetics, Vol. 21, No. 22, dds339, 01.11.2012, p. 5010-5018.

Research output: Contribution to journalArticle

Song, Y, Yeung, E, Liu, A, Vanderweele, TJ, Chen, L, Lu, C, Liu, C, Schisterman, EF, Ning, Y & Zhang, C 2012, 'Pancreatic beta-cell function and type 2 diabetes risk: Quantify the causal effect using a Mendelian randomization approach based on meta-analyses', Human Molecular Genetics, vol. 21, no. 22, dds339, pp. 5010-5018. https://doi.org/10.1093/hmg/dds339
Song, Yiqing ; Yeung, Edwina ; Liu, Aiyi ; Vanderweele, Tyler J. ; Chen, Liwei ; Lu, Chen ; Liu, Chunling ; Schisterman, Enrique F. ; Ning, Yi ; Zhang, Cuilin. / Pancreatic beta-cell function and type 2 diabetes risk : Quantify the causal effect using a Mendelian randomization approach based on meta-analyses. In: Human Molecular Genetics. 2012 ; Vol. 21, No. 22. pp. 5010-5018.
@article{12451d8e3b144fcb8504c26010ae3e77,
title = "Pancreatic beta-cell function and type 2 diabetes risk: Quantify the causal effect using a Mendelian randomization approach based on meta-analyses",
abstract = "The objective of the study is to quantify the causal effect of β-cell function on type 2 diabetes by minimizing residual confounding and reverse causation. We employed a Mendelian randomization (MR) approach using TCF7L2 variant rs7903146 as an instrument for lifelong levels of β-cell function. We first conducted two sets of meta-analyses to quantify the association of the TCF7L2 variant with the risk of type 2 diabetes among 55 436 cases and 106 020 controls from 66 studies by calculating pooled odds ratio (OR) and to quantify the associations with multiple direct or indirect measures of β-cell function among 35 052 non-diabetic individuals from 31 studies by calculating pooled mean difference. We further applied the method of MR to obtain the causal estimates for the effect of β-cell function on type 2 diabetes risk based on findings from the meta-analyses. The OR [95{\%} confidence interval (CI)] was 0.87 (0.81-0.93) for each five unit increment in homeostasis model assessment of insulin secretion (HOMA-{\%}B) (P = 3.0 × 10-5). In addition, for measures based on intravenous glucose tolerance test, ORs (95{\%} CI) associated with type 2 diabetes risk were 0.24 (0.08-0.74) (P = 0.01) and 0.14 (0.04-0.48) (P = 0.002) for per 1 standard deviation increment in insulin sensitivity index and disposition index, respectively. Findings from the present study lend support to a causal role of pancreatic β-cell function itself in the etiology of type 2 diabetes.",
author = "Yiqing Song and Edwina Yeung and Aiyi Liu and Vanderweele, {Tyler J.} and Liwei Chen and Chen Lu and Chunling Liu and Schisterman, {Enrique F.} and Yi Ning and Cuilin Zhang",
year = "2012",
month = "11",
day = "1",
doi = "10.1093/hmg/dds339",
language = "English (US)",
volume = "21",
pages = "5010--5018",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "22",

}

TY - JOUR

T1 - Pancreatic beta-cell function and type 2 diabetes risk

T2 - Quantify the causal effect using a Mendelian randomization approach based on meta-analyses

AU - Song, Yiqing

AU - Yeung, Edwina

AU - Liu, Aiyi

AU - Vanderweele, Tyler J.

AU - Chen, Liwei

AU - Lu, Chen

AU - Liu, Chunling

AU - Schisterman, Enrique F.

AU - Ning, Yi

AU - Zhang, Cuilin

PY - 2012/11/1

Y1 - 2012/11/1

N2 - The objective of the study is to quantify the causal effect of β-cell function on type 2 diabetes by minimizing residual confounding and reverse causation. We employed a Mendelian randomization (MR) approach using TCF7L2 variant rs7903146 as an instrument for lifelong levels of β-cell function. We first conducted two sets of meta-analyses to quantify the association of the TCF7L2 variant with the risk of type 2 diabetes among 55 436 cases and 106 020 controls from 66 studies by calculating pooled odds ratio (OR) and to quantify the associations with multiple direct or indirect measures of β-cell function among 35 052 non-diabetic individuals from 31 studies by calculating pooled mean difference. We further applied the method of MR to obtain the causal estimates for the effect of β-cell function on type 2 diabetes risk based on findings from the meta-analyses. The OR [95% confidence interval (CI)] was 0.87 (0.81-0.93) for each five unit increment in homeostasis model assessment of insulin secretion (HOMA-%B) (P = 3.0 × 10-5). In addition, for measures based on intravenous glucose tolerance test, ORs (95% CI) associated with type 2 diabetes risk were 0.24 (0.08-0.74) (P = 0.01) and 0.14 (0.04-0.48) (P = 0.002) for per 1 standard deviation increment in insulin sensitivity index and disposition index, respectively. Findings from the present study lend support to a causal role of pancreatic β-cell function itself in the etiology of type 2 diabetes.

AB - The objective of the study is to quantify the causal effect of β-cell function on type 2 diabetes by minimizing residual confounding and reverse causation. We employed a Mendelian randomization (MR) approach using TCF7L2 variant rs7903146 as an instrument for lifelong levels of β-cell function. We first conducted two sets of meta-analyses to quantify the association of the TCF7L2 variant with the risk of type 2 diabetes among 55 436 cases and 106 020 controls from 66 studies by calculating pooled odds ratio (OR) and to quantify the associations with multiple direct or indirect measures of β-cell function among 35 052 non-diabetic individuals from 31 studies by calculating pooled mean difference. We further applied the method of MR to obtain the causal estimates for the effect of β-cell function on type 2 diabetes risk based on findings from the meta-analyses. The OR [95% confidence interval (CI)] was 0.87 (0.81-0.93) for each five unit increment in homeostasis model assessment of insulin secretion (HOMA-%B) (P = 3.0 × 10-5). In addition, for measures based on intravenous glucose tolerance test, ORs (95% CI) associated with type 2 diabetes risk were 0.24 (0.08-0.74) (P = 0.01) and 0.14 (0.04-0.48) (P = 0.002) for per 1 standard deviation increment in insulin sensitivity index and disposition index, respectively. Findings from the present study lend support to a causal role of pancreatic β-cell function itself in the etiology of type 2 diabetes.

UR - http://www.scopus.com/inward/record.url?scp=84868143292&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84868143292&partnerID=8YFLogxK

U2 - 10.1093/hmg/dds339

DO - 10.1093/hmg/dds339

M3 - Article

VL - 21

SP - 5010

EP - 5018

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 22

M1 - dds339

ER -