Publication

Bilirubin as a potential causal factor in type 2 diabetes risk: a Mendelian randomization study

Abbasi, A., Deetman, P. E., Corpeleijn, E., Gansevoort, R. T., Gans, R. O. B., Hillege, H. L., van der Harst, P., Stolk, R. P., Navis, G., Alizadeh, B. Z. & Bakker, S. J. L., Apr-2015, In : Diabetes. 64, 4, p. 1459-1469 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Abbasi, A., Deetman, P. E., Corpeleijn, E., Gansevoort, R. T., Gans, R. O. B., Hillege, H. L., ... Bakker, S. J. L. (2015). Bilirubin as a potential causal factor in type 2 diabetes risk: a Mendelian randomization study. Diabetes, 64(4), 1459-1469. https://doi.org/10.2337/db14-0228

Author

Abbasi, Ali ; Deetman, Petronella E. ; Corpeleijn, Eva ; Gansevoort, Ron T. ; Gans, Rijk O. B. ; Hillege, Hans L. ; van der Harst, Pim ; Stolk, Ronald P. ; Navis, Gerjan ; Alizadeh, Behrooz Z. ; Bakker, Stephan J. L. / Bilirubin as a potential causal factor in type 2 diabetes risk : a Mendelian randomization study. In: Diabetes. 2015 ; Vol. 64, No. 4. pp. 1459-1469.

Harvard

Abbasi, A, Deetman, PE, Corpeleijn, E, Gansevoort, RT, Gans, ROB, Hillege, HL, van der Harst, P, Stolk, RP, Navis, G, Alizadeh, BZ & Bakker, SJL 2015, 'Bilirubin as a potential causal factor in type 2 diabetes risk: a Mendelian randomization study', Diabetes, vol. 64, no. 4, pp. 1459-1469. https://doi.org/10.2337/db14-0228

Standard

Bilirubin as a potential causal factor in type 2 diabetes risk : a Mendelian randomization study. / Abbasi, Ali; Deetman, Petronella E.; Corpeleijn, Eva; Gansevoort, Ron T.; Gans, Rijk O. B.; Hillege, Hans L.; van der Harst, Pim; Stolk, Ronald P.; Navis, Gerjan; Alizadeh, Behrooz Z.; Bakker, Stephan J. L.

In: Diabetes, Vol. 64, No. 4, 04.2015, p. 1459-1469.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Abbasi A, Deetman PE, Corpeleijn E, Gansevoort RT, Gans ROB, Hillege HL et al. Bilirubin as a potential causal factor in type 2 diabetes risk: a Mendelian randomization study. Diabetes. 2015 Apr;64(4):1459-1469. https://doi.org/10.2337/db14-0228


BibTeX

@article{e6b2bf66423a4e73a428381256ca3b3c,
title = "Bilirubin as a potential causal factor in type 2 diabetes risk: a Mendelian randomization study",
abstract = "Circulating bilirubin, a natural antioxidant, is associated with decreased risk of type 2 diabetes (T2D), but the nature of the relationship remains unknown. We performed Mendelian randomization in a prospective cohort of 3,381 participants free of diabetes at baseline (aged 28-75 years; women, 52.6{\%}). We used rs6742078 located in UDP-glucuronosyltransferase (UGT1A1) locus as instrumental variable (IV) to study a potential causal effect of serum total bilirubin on T2D risk. A total of 210 (6.2{\%}) participants developed T2D during a median follow-up of 7.8 years. In adjusted analyses, rs6742078, which explained 19.5{\%} of bilirubin variation, was strongly associated with total bilirubin (a 0.68-SD increase in bilirubin levels per T allele; P<1×10(-122)) and was also associated with T2D risk (OR 0.69 [95{\%}CI, 0.54-0.90]; P=0.006). Per 1-SD increase in log-transformed bilirubin levels, we observed a 25{\%} (OR 0.75 [95{\%}CI, 0.62-0.92]; P=0.004) lower risk of T2D. In Mendelian randomization analysis, the causal risk reduction for T2D was estimated to be 42{\%} (causal ORIVestimation per 1-SD increase in log-transformed bilirubin 0.58 [95{\%}CI, 0.39-0.84]; P=0.005), which was comparable to the observational estimate (Durbin-Wu-Hausman chi-square test Pfor difference =0.19). These novel results provide evidence that elevated bilirubin is causally associated with risk of T2D and support its role as a protective determinant.",
keywords = "MULTIPLE GENETIC-VARIANTS, GENOME-WIDE ASSOCIATION, OXIDATIVE STRESS, SERUM BILIRUBIN, METABOLIC SYNDROME, COMMON VARIANTS, HEART-DISEASE, HYPERBILIRUBINEMIA, MORTALITY, GLUCOSE",
author = "Ali Abbasi and Deetman, {Petronella E.} and Eva Corpeleijn and Gansevoort, {Ron T.} and Gans, {Rijk O. B.} and Hillege, {Hans L.} and {van der Harst}, Pim and Stolk, {Ronald P.} and Gerjan Navis and Alizadeh, {Behrooz Z.} and Bakker, {Stephan J. L.}",
note = "{\circledC} 2014 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 = "4",
doi = "10.2337/db14-0228",
language = "English",
volume = "64",
pages = "1459--1469",
journal = "Diabetes",
issn = "0012-1797",
publisher = "AMER DIABETES ASSOC",
number = "4",

}

RIS

TY - JOUR

T1 - Bilirubin as a potential causal factor in type 2 diabetes risk

T2 - a Mendelian randomization study

AU - Abbasi, Ali

AU - Deetman, Petronella E.

AU - Corpeleijn, Eva

AU - Gansevoort, Ron T.

AU - Gans, Rijk O. B.

AU - Hillege, Hans L.

AU - van der Harst, Pim

AU - Stolk, Ronald P.

AU - Navis, Gerjan

AU - Alizadeh, Behrooz Z.

AU - Bakker, Stephan J. L.

N1 - © 2014 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 - 2015/4

Y1 - 2015/4

N2 - Circulating bilirubin, a natural antioxidant, is associated with decreased risk of type 2 diabetes (T2D), but the nature of the relationship remains unknown. We performed Mendelian randomization in a prospective cohort of 3,381 participants free of diabetes at baseline (aged 28-75 years; women, 52.6%). We used rs6742078 located in UDP-glucuronosyltransferase (UGT1A1) locus as instrumental variable (IV) to study a potential causal effect of serum total bilirubin on T2D risk. A total of 210 (6.2%) participants developed T2D during a median follow-up of 7.8 years. In adjusted analyses, rs6742078, which explained 19.5% of bilirubin variation, was strongly associated with total bilirubin (a 0.68-SD increase in bilirubin levels per T allele; P<1×10(-122)) and was also associated with T2D risk (OR 0.69 [95%CI, 0.54-0.90]; P=0.006). Per 1-SD increase in log-transformed bilirubin levels, we observed a 25% (OR 0.75 [95%CI, 0.62-0.92]; P=0.004) lower risk of T2D. In Mendelian randomization analysis, the causal risk reduction for T2D was estimated to be 42% (causal ORIVestimation per 1-SD increase in log-transformed bilirubin 0.58 [95%CI, 0.39-0.84]; P=0.005), which was comparable to the observational estimate (Durbin-Wu-Hausman chi-square test Pfor difference =0.19). These novel results provide evidence that elevated bilirubin is causally associated with risk of T2D and support its role as a protective determinant.

AB - Circulating bilirubin, a natural antioxidant, is associated with decreased risk of type 2 diabetes (T2D), but the nature of the relationship remains unknown. We performed Mendelian randomization in a prospective cohort of 3,381 participants free of diabetes at baseline (aged 28-75 years; women, 52.6%). We used rs6742078 located in UDP-glucuronosyltransferase (UGT1A1) locus as instrumental variable (IV) to study a potential causal effect of serum total bilirubin on T2D risk. A total of 210 (6.2%) participants developed T2D during a median follow-up of 7.8 years. In adjusted analyses, rs6742078, which explained 19.5% of bilirubin variation, was strongly associated with total bilirubin (a 0.68-SD increase in bilirubin levels per T allele; P<1×10(-122)) and was also associated with T2D risk (OR 0.69 [95%CI, 0.54-0.90]; P=0.006). Per 1-SD increase in log-transformed bilirubin levels, we observed a 25% (OR 0.75 [95%CI, 0.62-0.92]; P=0.004) lower risk of T2D. In Mendelian randomization analysis, the causal risk reduction for T2D was estimated to be 42% (causal ORIVestimation per 1-SD increase in log-transformed bilirubin 0.58 [95%CI, 0.39-0.84]; P=0.005), which was comparable to the observational estimate (Durbin-Wu-Hausman chi-square test Pfor difference =0.19). These novel results provide evidence that elevated bilirubin is causally associated with risk of T2D and support its role as a protective determinant.

KW - MULTIPLE GENETIC-VARIANTS

KW - GENOME-WIDE ASSOCIATION

KW - OXIDATIVE STRESS

KW - SERUM BILIRUBIN

KW - METABOLIC SYNDROME

KW - COMMON VARIANTS

KW - HEART-DISEASE

KW - HYPERBILIRUBINEMIA

KW - MORTALITY

KW - GLUCOSE

U2 - 10.2337/db14-0228

DO - 10.2337/db14-0228

M3 - Article

VL - 64

SP - 1459

EP - 1469

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 4

ER -

ID: 14889549