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 - Räikkönen, 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 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.
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 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.
KW - Depression
KW - GWAS
KW - Meta-analysis
KW - Pleiotropy
KW - Type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85053407353&partnerID=8YFLogxK
U2 - 10.1097/PSY.0000000000000555
DO - 10.1097/PSY.0000000000000555
M3 - Article
C2 - 29280852
SN - 0033-3174
VL - 80
SP - 242
EP - 251
JO - Psychosomatic Medicine
JF - Psychosomatic Medicine
IS - 3
ER -