Shared genetics and bidirectional causal relationships between type 2 diabetes and attention-deficit/hyperactivity disorder  

作　　者：Ancha Baranova Vikas Chandhoke Hongbao Cao Fuquan Zhang 

机构地区：[1]School of Systems Biology,George Mason University,Fairfax,Virginia,USA [2]Research Centre for Medical Genetics,Moscow,Russian Federation [3]Institute of Neuropsychiatry,The Affiliated Brain Hospital of Nanjing Medical University,Nanjing,Jiangsu,China [4]Department of Psychiatry,The Affiliated Brain Hospital of Nanjing Medical University,Nanjing,Jiangsu,China

出　　处：《General Psychiatry》2023年第2期106-113,共8页综合精神医学（英文）

摘　　要：Background Type 2 diabetes(T2D)is a chronic metabolic disorder with high comorbidity with mental disorders.The genetic links between attention-deficit/hyperactivity disorder(ADHD)and T2D have yet to be elucidated.Aims We aim to assess shared genetics and potential associations between ADHD and T2D.Methods We performed genetic correlation,two-sample Mendelian randomisation and polygenic overlap analyses between ADHD and T2D.The genome-wide association study(GWAS)summary results of T2D(80154 cases and 853816 controls),ADHD2019(20183 cases and 35191 controls from the 2019 GWAS ADHD dataset)and ADHD2022(38691 cases and 275986 controls from the 2022 GWAS ADHD dataset)were used for the analyses.The T2D dataset was obtained from the DIAGRAM Consortium.The ADHD datasets were obtained from the Psychiatric Genomics Consortium.We compared genome-wide association signals to reveal shared genetic variation between T2D and ADHD using the larger ADHD2022 dataset.Moreover,molecular pathways were constructed based on large-scale literature data to understand the connection between ADHD and T2D.Results T2D has positive genetic correlations with ADHD2019(rg=0.33)and ADHD2022(rg=0.31).Genetic liability to ADHD2019 was associated with an increased risk for T2D(odds ratio(OR):1.30,p<0.001),while genetic liability to ADHD2022 had a suggestive causal effect on T2D(OR:1.30,p=0.086).Genetic liability to T2D was associated with a higher risk for ADHD2019(OR:1.05,p=0.001)and ADHD2022(OR:1.03,p<0.001).The polygenic overlap analysis showed that most causal variants of T2D are shared with ADHD2022.T2D and ADHD2022 have three overlapping loci.Molecular pathway analysis suggests that ADHD and T2D could promote the risk of each other through inflammatory pathways.Conclusions Our study demonstrates substantial shared genetics and bidirectional causal associations between ADHD and T2D.

关 键 词：diabetes OVERLAP CAUSAL 

分 类 号：R587.1[医药卫生—内分泌] R749.94[医药卫生—内科学]