Publication

Bivariate Genome-Wide Association Study of Depressive Symptoms With Type 2 Diabetes and Quantitative Glycemic Traits

Haljas, K., Amare, A. T., Alizadeh, B. Z., Hsu, Y-H., Mosley, T., Newman, A., Murabito, J., Tiemeier, H., Tanaka, T., van Duijn, C., Ding, J., Llewellyn, D. J., Bennett, D. A., Terracciano, A., Launer, L., Ladwig, K-H., Cornelis, M. C., Teumer, A., Grabe, H., Kardia, S. L. R., Ware, E. B., Smith, J. A., Snieder, H., Eriksson, J. G., Groop, L., Raikkonen, K. & Lahti, J., 1-Apr-2018, In : Psychosomatic Medicine. 80, 3, p. 242-251 10 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Haljas, K., Amare, A. T., Alizadeh, B. Z., Hsu, Y-H., Mosley, T., Newman, A., ... Lahti, J. (2018). Bivariate Genome-Wide Association Study of Depressive Symptoms With Type 2 Diabetes and Quantitative Glycemic Traits. Psychosomatic Medicine, 80(3), 242-251. https://doi.org/10.1097/PSY.0000000000000555

Author

Haljas, Kadri ; Amare, Azmeraw T. ; Alizadeh, Behrooz Z. ; Hsu, Yi-Hsiang ; Mosley, Thomas ; Newman, Anne ; Murabito, Joanne ; Tiemeier, Henning ; Tanaka, Toshiko ; van Duijn, Cornelia ; Ding, Jingzhong ; Llewellyn, David J. ; Bennett, David A. ; Terracciano, Antonio ; Launer, Lenore ; Ladwig, Karl-Heinz ; Cornelis, Marylin C. ; Teumer, Alexander ; Grabe, Hans ; Kardia, Sharon L. R. ; Ware, Erin B. ; Smith, Jennifer A. ; Snieder, Harold ; Eriksson, Johan G. ; Groop, Leif ; Raikkonen, Katri ; Lahti, Jari. / Bivariate Genome-Wide Association Study of Depressive Symptoms With Type 2 Diabetes and Quantitative Glycemic Traits. In: Psychosomatic Medicine. 2018 ; Vol. 80, No. 3. pp. 242-251.

Harvard

Haljas, K, Amare, AT, Alizadeh, BZ, Hsu, Y-H, Mosley, T, Newman, A, Murabito, J, Tiemeier, H, Tanaka, T, van Duijn, C, Ding, J, Llewellyn, DJ, Bennett, DA, Terracciano, A, Launer, L, Ladwig, K-H, Cornelis, MC, Teumer, A, Grabe, H, Kardia, SLR, Ware, EB, Smith, JA, Snieder, H, Eriksson, JG, Groop, L, Raikkonen, K & Lahti, J 2018, 'Bivariate Genome-Wide Association Study of Depressive Symptoms With Type 2 Diabetes and Quantitative Glycemic Traits' Psychosomatic Medicine, vol. 80, no. 3, pp. 242-251. https://doi.org/10.1097/PSY.0000000000000555

Standard

Bivariate Genome-Wide Association Study of Depressive Symptoms With Type 2 Diabetes and Quantitative Glycemic Traits. / Haljas, Kadri; Amare, Azmeraw T.; Alizadeh, Behrooz Z.; Hsu, Yi-Hsiang; Mosley, Thomas; Newman, Anne; Murabito, Joanne; Tiemeier, Henning; Tanaka, Toshiko; van Duijn, Cornelia; Ding, Jingzhong; Llewellyn, David J.; Bennett, David A.; Terracciano, Antonio; Launer, Lenore; Ladwig, Karl-Heinz; Cornelis, Marylin C.; Teumer, Alexander; Grabe, Hans; Kardia, Sharon L. R.; Ware, Erin B.; Smith, Jennifer A.; Snieder, Harold; Eriksson, Johan G.; Groop, Leif; Raikkonen, Katri; Lahti, Jari.

In: Psychosomatic Medicine, Vol. 80, No. 3, 01.04.2018, p. 242-251.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Haljas K, Amare AT, Alizadeh BZ, Hsu Y-H, Mosley T, Newman A et al. Bivariate Genome-Wide Association Study of Depressive Symptoms With Type 2 Diabetes and Quantitative Glycemic Traits. Psychosomatic Medicine. 2018 Apr 1;80(3):242-251. https://doi.org/10.1097/PSY.0000000000000555


BibTeX

@article{b4dbb566ffaf4775ad13dce76ea372de,
title = "Bivariate Genome-Wide Association Study of Depressive Symptoms With Type 2 Diabetes and Quantitative Glycemic Traits",
abstract = "Objective: Shared genetic background may explain phenotypic associations between depression and Type 2 diabetes (T2D). We aimed to study, on a genome-wide level, if genetic correlation and pleiotropic loci exist between depressive symptoms and T2D or glycemic traits.Methods: We estimated single-nucleotide polymorphism (SNP)-based heritability and analyzed genetic correlation between depressive symptoms and T2D and glycemic traits with the linkage disequilibrium score regression by combining summary statistics of previously conducted-meta-analyses for depressive symptoms by CHARGE consortium (N = 51,258), T2D by DIAGRAM consortium (N = 34,840 patients and 114,981 controls), fasting glucose, fasting insulin, and homeostatic model assessment of beta-cell function and insulin resistance by MAGIC consortium (N = 58,074). Finally, we investigated pleiotropic loci using a bivariate genome-wide association study approach with summary statistics from genome-wide association study meta-analyses and reported loci with genome-wide significant bivariate association p value (p <5 x 10(-8)). Biological annotation and function of significant pleiotropic SNPs were assessed in several databases.Results: The SNP-based heritability ranged from 0.04 to 0.10 in each individual trait. In the linkage disequilibrium score regression analyses, depressive symptoms showed no significant genetic correlation with T2D or glycemic traits (p > 0.37). However, we identified pleiotropic genetic variations for depressive symptoms and T2D (in the IGF2BP2, CDKAL1, CDKN2B-AS, and PLEKHA1 genes), and fasting glucose (in the MADD, CDKN2B-AS, PEX16, and MTNR1B genes).Conclusions: We found no significant overall genetic correlations between depressive symptoms, T2D, or glycemic traits suggesting major differences in underlying biology of these traits. However, several potential pleiotropic loci were identified between depressive symptoms, T2D, and fasting glucose, suggesting that previously established phenotypic associations may be partly explained by genetic variation in these specific loci.",
keywords = "depression, meta-analysis, Type 2 diabetes, pleiotropy, GWAS, FATIGUE SYNDROME/MYALGIC ENCEPHALOMYELITIS, SINGLE-NUCLEOTIDE POLYMORPHISMS, GENE-EXPRESSION SUBTYPES, MAJOR DEPRESSION, RISK-FACTOR, SUSCEPTIBILITY LOCI, INSULIN-RESISTANCE, BIPOLAR DISORDER, FASTING GLUCOSE, METAANALYSIS",
author = "Kadri Haljas and Amare, {Azmeraw T.} and Alizadeh, {Behrooz Z.} and Yi-Hsiang Hsu and Thomas Mosley and Anne Newman and Joanne Murabito and Henning Tiemeier and Toshiko Tanaka and {van Duijn}, Cornelia and Jingzhong Ding and Llewellyn, {David J.} and Bennett, {David A.} and Antonio Terracciano and Lenore Launer and Karl-Heinz Ladwig and Cornelis, {Marylin C.} and Alexander Teumer and Hans Grabe and Kardia, {Sharon L. R.} and Ware, {Erin B.} and Smith, {Jennifer A.} and Harold Snieder and Eriksson, {Johan G.} and Leif Groop and Katri Raikkonen and Jari Lahti",
year = "2018",
month = "4",
day = "1",
doi = "10.1097/PSY.0000000000000555",
language = "English",
volume = "80",
pages = "242--251",
journal = "Psychosomatic Medicine",
issn = "0033-3174",
publisher = "LIPPINCOTT WILLIAMS & WILKINS",
number = "3",

}

RIS

TY - JOUR

T1 - Bivariate Genome-Wide Association Study of Depressive Symptoms With Type 2 Diabetes and Quantitative Glycemic Traits

AU - Haljas, Kadri

AU - Amare, Azmeraw T.

AU - Alizadeh, Behrooz Z.

AU - Hsu, Yi-Hsiang

AU - Mosley, Thomas

AU - Newman, Anne

AU - Murabito, Joanne

AU - Tiemeier, Henning

AU - Tanaka, Toshiko

AU - van Duijn, Cornelia

AU - Ding, Jingzhong

AU - Llewellyn, David J.

AU - Bennett, David A.

AU - Terracciano, Antonio

AU - Launer, Lenore

AU - Ladwig, Karl-Heinz

AU - Cornelis, Marylin C.

AU - Teumer, Alexander

AU - Grabe, Hans

AU - Kardia, Sharon L. R.

AU - Ware, Erin B.

AU - Smith, Jennifer A.

AU - Snieder, Harold

AU - Eriksson, Johan G.

AU - Groop, Leif

AU - Raikkonen, Katri

AU - Lahti, Jari

PY - 2018/4/1

Y1 - 2018/4/1

N2 - Objective: Shared genetic background may explain phenotypic associations between depression and Type 2 diabetes (T2D). We aimed to study, on a genome-wide level, if genetic correlation and pleiotropic loci exist between depressive symptoms and T2D or glycemic traits.Methods: We estimated single-nucleotide polymorphism (SNP)-based heritability and analyzed genetic correlation between depressive symptoms and T2D and glycemic traits with the linkage disequilibrium score regression by combining summary statistics of previously conducted-meta-analyses for depressive symptoms by CHARGE consortium (N = 51,258), T2D by DIAGRAM consortium (N = 34,840 patients and 114,981 controls), fasting glucose, fasting insulin, and homeostatic model assessment of beta-cell function and insulin resistance by MAGIC consortium (N = 58,074). Finally, we investigated pleiotropic loci using a bivariate genome-wide association study approach with summary statistics from genome-wide association study meta-analyses and reported loci with genome-wide significant bivariate association p value (p <5 x 10(-8)). Biological annotation and function of significant pleiotropic SNPs were assessed in several databases.Results: The SNP-based heritability ranged from 0.04 to 0.10 in each individual trait. In the linkage disequilibrium score regression analyses, depressive symptoms showed no significant genetic correlation with T2D or glycemic traits (p > 0.37). However, we identified pleiotropic genetic variations for depressive symptoms and T2D (in the IGF2BP2, CDKAL1, CDKN2B-AS, and PLEKHA1 genes), and fasting glucose (in the MADD, CDKN2B-AS, PEX16, and MTNR1B genes).Conclusions: We found no significant overall genetic correlations between depressive symptoms, T2D, or glycemic traits suggesting major differences in underlying biology of these traits. However, several potential pleiotropic loci were identified between depressive symptoms, T2D, and fasting glucose, suggesting that previously established phenotypic associations may be partly explained by genetic variation in these specific loci.

AB - Objective: Shared genetic background may explain phenotypic associations between depression and Type 2 diabetes (T2D). We aimed to study, on a genome-wide level, if genetic correlation and pleiotropic loci exist between depressive symptoms and T2D or glycemic traits.Methods: We estimated single-nucleotide polymorphism (SNP)-based heritability and analyzed genetic correlation between depressive symptoms and T2D and glycemic traits with the linkage disequilibrium score regression by combining summary statistics of previously conducted-meta-analyses for depressive symptoms by CHARGE consortium (N = 51,258), T2D by DIAGRAM consortium (N = 34,840 patients and 114,981 controls), fasting glucose, fasting insulin, and homeostatic model assessment of beta-cell function and insulin resistance by MAGIC consortium (N = 58,074). Finally, we investigated pleiotropic loci using a bivariate genome-wide association study approach with summary statistics from genome-wide association study meta-analyses and reported loci with genome-wide significant bivariate association p value (p <5 x 10(-8)). Biological annotation and function of significant pleiotropic SNPs were assessed in several databases.Results: The SNP-based heritability ranged from 0.04 to 0.10 in each individual trait. In the linkage disequilibrium score regression analyses, depressive symptoms showed no significant genetic correlation with T2D or glycemic traits (p > 0.37). However, we identified pleiotropic genetic variations for depressive symptoms and T2D (in the IGF2BP2, CDKAL1, CDKN2B-AS, and PLEKHA1 genes), and fasting glucose (in the MADD, CDKN2B-AS, PEX16, and MTNR1B genes).Conclusions: We found no significant overall genetic correlations between depressive symptoms, T2D, or glycemic traits suggesting major differences in underlying biology of these traits. However, several potential pleiotropic loci were identified between depressive symptoms, T2D, and fasting glucose, suggesting that previously established phenotypic associations may be partly explained by genetic variation in these specific loci.

KW - depression

KW - meta-analysis

KW - Type 2 diabetes

KW - pleiotropy

KW - GWAS

KW - FATIGUE SYNDROME/MYALGIC ENCEPHALOMYELITIS

KW - SINGLE-NUCLEOTIDE POLYMORPHISMS

KW - GENE-EXPRESSION SUBTYPES

KW - MAJOR DEPRESSION

KW - RISK-FACTOR

KW - SUSCEPTIBILITY LOCI

KW - INSULIN-RESISTANCE

KW - BIPOLAR DISORDER

KW - FASTING GLUCOSE

KW - METAANALYSIS

U2 - 10.1097/PSY.0000000000000555

DO - 10.1097/PSY.0000000000000555

M3 - Article

VL - 80

SP - 242

EP - 251

JO - Psychosomatic Medicine

JF - Psychosomatic Medicine

SN - 0033-3174

IS - 3

ER -

ID: 65133347