Genetic underpinning of the comorbidity between type 2 diabetes and osteoarthritis.
Genetic underpinning of the comorbidity between type 2 diabetes and osteoarthritis.
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DOI：
10.1016/j.ajhg.2023.06.010
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发表时间：
2023-08-03
影响因子：
9.8
通讯作者：
中科院分区：
文献类型：
--
作者：
多发病是一个日益严重的公共卫生挑战，对卫生管理和政策具有重要影响。最常见的多发病模式是心脏代谢和骨关节疾病的组合。在这里，我们研究了2型糖尿病和骨关节炎之间共病的遗传基础。我们发现这两种疾病之间存在全基因组遗传相关性，并在18个基因组区域发现了关联信号共定位的有力证据。我们整合了多组学和功能信息，以解决共定位信号并识别高置信度的效应基因，包括FTO和IRX 3，这为肥胖和这两种疾病之间的流行病学联系提供了概念验证。我们发现脂质代谢和骨骼形成途径的信号富集分别支持膝关节和髋关节骨关节炎合并2型糖尿病。因果推理分析确定了组织特异性基因表达对合并症结局的复杂影响。我们的研究结果为2型糖尿病-骨关节炎疾病共同发生的生物学基础提供了见解。多发性硬化症是一个日益严重的公共卫生挑战。在这里，我们研究了2型糖尿病和骨关节炎之间共病的遗传基础，并提供了其生物学基础的见解。该方法可以应用于任何一对共同发生的疾病。
Multimorbidity is a rising public health challenge with important implications for health management and policy. The most common multimorbidity pattern is the combination of cardiometabolic and osteoarticular diseases. Here, we study the genetic underpinning of the comorbidity between type 2 diabetes and osteoarthritis. We find genome-wide genetic correlation between the two diseases and robust evidence for association-signal colocalization at 18 genomic regions. We integrate multi-omics and functional information to resolve the colocalizing signals and identify high-confidence effector genes, including FTO and IRX3, which provide proof-of-concept insights into the epidemiologic link between obesity and both diseases. We find enrichment for lipid metabolism and skeletal formation pathways for signals underpinning the knee and hip osteoarthritis comorbidities with type 2 diabetes, respectively. Causal inference analysis identifies complex effects of tissue-specific gene expression on comorbidity outcomes. Our findings provide insights into the biological basis for the type 2 diabetes-osteoarthritis disease co-occurrence. Multimorbidity is a rising public health challenge. Here, we study the genetic underpinning of the comorbidity between type 2 diabetes and osteoarthritis and provide insights into its biological basis. The approach can be applied to any pair of co-occurring diseases.
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影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
14.9
作者：
Gillespie M;Jassal B;Stephan R;Milacic M;Rothfels K;Senff-Ribeiro A;Griss J;Sevilla C;Matthews L;Gong C;Deng C;Varusai T;Ragueneau E;Haider Y;May B;Shamovsky V;Weiser J;Brunson T;Sanati N;Beckman L;Shao X;Fabregat A;Sidiropoulos K;Murillo J;Viteri G;Cook J;Shorser S;Bader G;Demir E;Sander C;Haw R;Wu G;Stein L;Hermjakob H;D'Eustachio P
通讯作者：
D'Eustachio P
影响因子：
17.1
作者：
Finan C;Gaulton A;Kruger FA;Lumbers RT;Shah T;Engmann J;Galver L;Kelley R;Karlsson A;Santos R;Overington JP;Hingorani AD;Casas JP
通讯作者：
Casas JP