Genetic variants of gestational diabetes mellitus: a study of 112 SNPs among 8722 women in two independent populations

Ming Ding; Jorge Chavarro; Sjurdur Olsen; Yuan Lin; Sylvia H Ley; Wei Bao; Shristi Rawal; Louise G Grunnet; Anne Cathrine B Thuesen; James L Mills; Edwina Yeung; Stefanie N Hinkle; Wei Zhang; Allan Vaag; Aiyi Liu; Frank B Hu; Cuilin Zhang

doi:10.1007/s00125-018-4637-8

Genetic variants of gestational diabetes mellitus: a study of 112 SNPs among 8722 women in two independent populations

Ming Ding, Jorge Chavarro, Sjurdur Olsen, Yuan Lin, Sylvia H Ley, Wei Bao, Shristi Rawal, Louise G Grunnet, Anne Cathrine B Thuesen, James L Mills, Edwina Yeung, Stefanie N Hinkle, Wei Zhang, Allan Vaag, Aiyi Liu, Frank B Hu, Cuilin Zhang

35 Citations (Scopus)

Abstract

AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is a common complication of pregnancy that has substantial short- and long-term adverse health implications for women and their children. However, large-scale studies on genetic risk loci for GDM remain sparse.

METHODS: We conducted a case-control study among 2636 women with GDM and 6086 non-GDM control women from the Nurses' Health Study II and the Danish National Birth Cohort. A total of 112 susceptibility genetic variants confirmed by genome-wide association studies for type 2 diabetes were selected and measured. A weighted genetic risk score (GRS) was created based on variants that were significantly associated with risk of GDM after correcting for the false discovery rate.

RESULTS: For the first time, we identified eight variants associated with GDM, namely rs7957197 (HNF1A), rs10814916 (GLIS3), rs3802177 (SLC30A8), rs9379084 (RREB1), rs34872471 (TCF7L2), rs7903146 (TCF7L2), rs11787792 (GPSM1) and rs7041847 (GLIS3). In addition, we confirmed three variants, rs10830963 (MTNR1B), rs1387153 (MTNR1B) and rs4506565 (TCF7L2), that had previously been significantly associated with GDM risk. Furthermore, compared with participants in the first (lowest) quartile of weighted GRS based on these 11 SNPs, the ORs for GDM were 1.07 (95% CI 0.93, 1.22), 1.23 (95% CI 1.07, 1.41) and 1.53 (95% CI 1.34, 1.74) for participants in the second, third and fourth (highest) quartiles, respectively. The significant positive associations between the weighted GRS and risk of GDM persisted across most of the strata of major risk factors for GDM, including family history of type 2 diabetes, smoking status, BMI and age.

CONCLUSIONS/INTERPRETATION: In this large-scale case-control study with women from two independent populations, eight novel GDM SNPs were identified. These findings offer the potential to improve our understanding of the aetiology of GDM, and particularly of biological mechanisms related to beta cell function.

Original language	English
Journal	Diabetologia
Volume	61
Issue number	8
Pages (from-to)	1758-1768
Number of pages	11
ISSN	0012-186X
DOIs	https://doi.org/10.1007/s00125-018-4637-8
Publication status	Published - 1 Aug 2018
Externally published	Yes

Keywords

Adult
Alleles
Case-Control Studies
Diabetes Mellitus, Type 2/genetics
Diabetes, Gestational/genetics
Family Health
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Humans
Middle Aged
Polymorphism, Single Nucleotide
Pregnancy
Risk Factors

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Ding, M., Chavarro, J., Olsen, S., Lin, Y., Ley, S. H., Bao, W., Rawal, S., Grunnet, L. G., Thuesen, A. C. B., Mills, J. L., Yeung, E., Hinkle, S. N., Zhang, W., Vaag, A., Liu, A., Hu, F. B., & Zhang, C. (2018). Genetic variants of gestational diabetes mellitus: a study of 112 SNPs among 8722 women in two independent populations. Diabetologia, 61(8), 1758-1768. https://doi.org/10.1007/s00125-018-4637-8

Ding, M, Chavarro, J, Olsen, S, Lin, Y, Ley, SH, Bao, W, Rawal, S, Grunnet, LG, Thuesen, ACB, Mills, JL, Yeung, E, Hinkle, SN, Zhang, W, Vaag, A, Liu, A, Hu, FB & Zhang, C 2018, 'Genetic variants of gestational diabetes mellitus: a study of 112 SNPs among 8722 women in two independent populations', Diabetologia, vol. 61, no. 8, pp. 1758-1768. https://doi.org/10.1007/s00125-018-4637-8

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title = "Genetic variants of gestational diabetes mellitus: a study of 112 SNPs among 8722 women in two independent populations",

abstract = "AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is a common complication of pregnancy that has substantial short- and long-term adverse health implications for women and their children. However, large-scale studies on genetic risk loci for GDM remain sparse.METHODS: We conducted a case-control study among 2636 women with GDM and 6086 non-GDM control women from the Nurses' Health Study II and the Danish National Birth Cohort. A total of 112 susceptibility genetic variants confirmed by genome-wide association studies for type 2 diabetes were selected and measured. A weighted genetic risk score (GRS) was created based on variants that were significantly associated with risk of GDM after correcting for the false discovery rate.RESULTS: For the first time, we identified eight variants associated with GDM, namely rs7957197 (HNF1A), rs10814916 (GLIS3), rs3802177 (SLC30A8), rs9379084 (RREB1), rs34872471 (TCF7L2), rs7903146 (TCF7L2), rs11787792 (GPSM1) and rs7041847 (GLIS3). In addition, we confirmed three variants, rs10830963 (MTNR1B), rs1387153 (MTNR1B) and rs4506565 (TCF7L2), that had previously been significantly associated with GDM risk. Furthermore, compared with participants in the first (lowest) quartile of weighted GRS based on these 11 SNPs, the ORs for GDM were 1.07 (95% CI 0.93, 1.22), 1.23 (95% CI 1.07, 1.41) and 1.53 (95% CI 1.34, 1.74) for participants in the second, third and fourth (highest) quartiles, respectively. The significant positive associations between the weighted GRS and risk of GDM persisted across most of the strata of major risk factors for GDM, including family history of type 2 diabetes, smoking status, BMI and age.CONCLUSIONS/INTERPRETATION: In this large-scale case-control study with women from two independent populations, eight novel GDM SNPs were identified. These findings offer the potential to improve our understanding of the aetiology of GDM, and particularly of biological mechanisms related to beta cell function.",

keywords = "Adult, Alleles, Case-Control Studies, Diabetes Mellitus, Type 2/genetics, Diabetes, Gestational/genetics, Family Health, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Middle Aged, Polymorphism, Single Nucleotide, Pregnancy, Risk Factors",

author = "Ming Ding and Jorge Chavarro and Sjurdur Olsen and Yuan Lin and Ley, {Sylvia H} and Wei Bao and Shristi Rawal and Grunnet, {Louise G} and Thuesen, {Anne Cathrine B} and Mills, {James L} and Edwina Yeung and Hinkle, {Stefanie N} and Wei Zhang and Allan Vaag and Aiyi Liu and Hu, {Frank B} and Cuilin Zhang",

year = "2018",

month = aug,

day = "1",

doi = "10.1007/s00125-018-4637-8",

language = "English",

volume = "61",

pages = "1758--1768",

journal = "Diabetologia",

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number = "8",

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TY - JOUR

T1 - Genetic variants of gestational diabetes mellitus

T2 - a study of 112 SNPs among 8722 women in two independent populations

AU - Ding, Ming

AU - Chavarro, Jorge

AU - Olsen, Sjurdur

AU - Lin, Yuan

AU - Ley, Sylvia H

AU - Bao, Wei

AU - Rawal, Shristi

AU - Grunnet, Louise G

AU - Thuesen, Anne Cathrine B

AU - Mills, James L

AU - Yeung, Edwina

AU - Hinkle, Stefanie N

AU - Zhang, Wei

AU - Vaag, Allan

AU - Liu, Aiyi

AU - Hu, Frank B

AU - Zhang, Cuilin

PY - 2018/8/1

Y1 - 2018/8/1

N2 - AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is a common complication of pregnancy that has substantial short- and long-term adverse health implications for women and their children. However, large-scale studies on genetic risk loci for GDM remain sparse.METHODS: We conducted a case-control study among 2636 women with GDM and 6086 non-GDM control women from the Nurses' Health Study II and the Danish National Birth Cohort. A total of 112 susceptibility genetic variants confirmed by genome-wide association studies for type 2 diabetes were selected and measured. A weighted genetic risk score (GRS) was created based on variants that were significantly associated with risk of GDM after correcting for the false discovery rate.RESULTS: For the first time, we identified eight variants associated with GDM, namely rs7957197 (HNF1A), rs10814916 (GLIS3), rs3802177 (SLC30A8), rs9379084 (RREB1), rs34872471 (TCF7L2), rs7903146 (TCF7L2), rs11787792 (GPSM1) and rs7041847 (GLIS3). In addition, we confirmed three variants, rs10830963 (MTNR1B), rs1387153 (MTNR1B) and rs4506565 (TCF7L2), that had previously been significantly associated with GDM risk. Furthermore, compared with participants in the first (lowest) quartile of weighted GRS based on these 11 SNPs, the ORs for GDM were 1.07 (95% CI 0.93, 1.22), 1.23 (95% CI 1.07, 1.41) and 1.53 (95% CI 1.34, 1.74) for participants in the second, third and fourth (highest) quartiles, respectively. The significant positive associations between the weighted GRS and risk of GDM persisted across most of the strata of major risk factors for GDM, including family history of type 2 diabetes, smoking status, BMI and age.CONCLUSIONS/INTERPRETATION: In this large-scale case-control study with women from two independent populations, eight novel GDM SNPs were identified. These findings offer the potential to improve our understanding of the aetiology of GDM, and particularly of biological mechanisms related to beta cell function.

AB - AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is a common complication of pregnancy that has substantial short- and long-term adverse health implications for women and their children. However, large-scale studies on genetic risk loci for GDM remain sparse.METHODS: We conducted a case-control study among 2636 women with GDM and 6086 non-GDM control women from the Nurses' Health Study II and the Danish National Birth Cohort. A total of 112 susceptibility genetic variants confirmed by genome-wide association studies for type 2 diabetes were selected and measured. A weighted genetic risk score (GRS) was created based on variants that were significantly associated with risk of GDM after correcting for the false discovery rate.RESULTS: For the first time, we identified eight variants associated with GDM, namely rs7957197 (HNF1A), rs10814916 (GLIS3), rs3802177 (SLC30A8), rs9379084 (RREB1), rs34872471 (TCF7L2), rs7903146 (TCF7L2), rs11787792 (GPSM1) and rs7041847 (GLIS3). In addition, we confirmed three variants, rs10830963 (MTNR1B), rs1387153 (MTNR1B) and rs4506565 (TCF7L2), that had previously been significantly associated with GDM risk. Furthermore, compared with participants in the first (lowest) quartile of weighted GRS based on these 11 SNPs, the ORs for GDM were 1.07 (95% CI 0.93, 1.22), 1.23 (95% CI 1.07, 1.41) and 1.53 (95% CI 1.34, 1.74) for participants in the second, third and fourth (highest) quartiles, respectively. The significant positive associations between the weighted GRS and risk of GDM persisted across most of the strata of major risk factors for GDM, including family history of type 2 diabetes, smoking status, BMI and age.CONCLUSIONS/INTERPRETATION: In this large-scale case-control study with women from two independent populations, eight novel GDM SNPs were identified. These findings offer the potential to improve our understanding of the aetiology of GDM, and particularly of biological mechanisms related to beta cell function.

KW - Adult

KW - Alleles

KW - Case-Control Studies

KW - Diabetes Mellitus, Type 2/genetics

KW - Diabetes, Gestational/genetics

KW - Family Health

KW - Female

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Pregnancy

KW - Risk Factors

U2 - 10.1007/s00125-018-4637-8

DO - 10.1007/s00125-018-4637-8

M3 - Journal article

C2 - 29947923

SN - 0012-186X

VL - 61

SP - 1758

EP - 1768

JO - Diabetologia

JF - Diabetologia

IS - 8

ER -

Genetic variants of gestational diabetes mellitus: a study of 112 SNPs among 8722 women in two independent populations

Abstract

Keywords

UN SDGs

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