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; Räikkönen, Katri; Lahti, Jari

doi:10.1097/PSY.0000000000000555

Benutzer: Gast

journal article

Titel:: Bivariate Genome-Wide Association Study of Depressive Symptoms With Type 2 Diabetes and Quantitative Glycemic Traits.
Dokumenttyp:: Article; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Autor(en):: 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; Räikkönen, Katri; Lahti, Jari
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 β-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 × 10). 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.
Zeitschriftentitel:: Psychosom Med
Jahr:: 2018
Band / Volume:: 80
Heft / Issue:: 3
Seitenangaben Beitrag:: 242-251
Volltext / DOI:: doi:10.1097/PSY.0000000000000555
PubMed:: http://view.ncbi.nlm.nih.gov/pubmed/29280852
Print-ISSN:: 0033-3174
TUM Einrichtung:: Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie
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mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie (Prof. Henningsen)2018