Genetic Correlation Analysis and Transcriptome-wide Association Study Suggest the Overlapped Genetic Mechanism between Gout and Attention-deficit Hyperactivity Disorder
Objectives: Gout is a common inflammatory arthritis, which is caused by hyperuricemia. Limited efforts have been paid to systematically explore the relationships between gout and common psychiatric disorders. Methods: Genome-wide association study summary data of gout were obtained from the GeneATLA...
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| Veröffentlicht in: | Canadian journal of psychiatry 2021-12, Vol.66 (12), p.1077-1084 |
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| container_title | Canadian journal of psychiatry |
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| creator | Kafle, Om Prakash Wang, Xi Cheng, Shiqiang Ding, Miao Li, Ping Cheng, Bolun Liang, Xiao Liu, Li Du, Yanan Ma, Mei Zhang, Lu Zhao, Yan Wen, Yan Zhang, Feng |
| description | Objectives:
Gout is a common inflammatory arthritis, which is caused by hyperuricemia. Limited efforts have been paid to systematically explore the relationships between gout and common psychiatric disorders.
Methods:
Genome-wide association study summary data of gout were obtained from the GeneATLAS, which contained 452,264 participants including 3,528 gout cases. Linkage disequilibrium score regression (LDSC) was first conducted to evaluate the genetic relationships between gout and 5 common psychiatric disorders. Transcriptome-wide association studies (TWAS) was then conducted to explore the potential biological mechanism underlying the observed genetic correlation between gout and attention-deficit hyperactivity disorder (ADHD). The Database for Annotation, Visualization and Integrated Discovery online functional annotation system was applied for pathway enrichment analysis and gene ontology enrichment analysis.
Results:
LDSC analysis observed significant genetic correlation between gout and ADHD (genetic correlation coefficients = 0.29, standard error = 0.09 and P value = 0.0015). Further TWAS of gout identified 105 genes with P value < 0.05 in muscle skeleton and 228 genes with P value < 0.05 in blood. TWAS of ADHD also detected 300 genes with P value < 0.05 in blood. Further comparing the TWAS results identified 9 common candidate genes shared by gout and ADHD, such as CD300C (P
gout = 0.0040; P
ADHD = 0.0226), KDM6B (P
gout = 0.0074; P
ADHD = 0.0460), and BST1 (P
gout = 0.0349; P
ADHD = 0.03560).
Conclusion:
We observed genetic correlation between gout and ADHD and identified multiple candidate genes for gout and ADHD. |
| doi_str_mv | 10.1177/0706743720970844 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8689453</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_0706743720970844</sage_id><sourcerecordid>2458036848</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3774-d6672fa7a7edab56735ccbf2464782aa8892534d2875c778b30c753d4693b4683</originalsourceid><addsrcrecordid>eNp1kk1v1DAQQCMEokvhzglZ4sIl4M_YuSCtFrpFKuqh5Rw59mTXVRIH29kq_4if2YRtC1TCFx_mzZvxeLLsLcEfCZHyE5a4kJxJikuJFefPshXhpcwxJuJ5tlrC-RI_yV7FeIPnQ6l6mZ0wRoRQlK2yX1voITmDNj4EaHVyvkfrXrdTdBHp3qLroPtoghuS7yC_dRbQOkZv3JG9SqOd0NW420FMKO0BXR4gtHoYwKIH-Xcwe9272KEa0i1Aj7Z-TL_165SgX0y5hcYZl9D5NEDQJrmDSxP64qIPFsLr7EWj2whv7u_T7MfZ1-vNeX5xuf22WV_khknJc1sUkjZaaglW16KQTBhTN5QXXCqqtVIlFYxbqqQwUqqaYSMFs7woWc0LxU6zz0fvMNYdWDM3F3RbDcF1OkyV1676N9K7fbXzh0oVquSCzYIP94Lgf47zUKrORQNtq3vwY6woFwqzQvGl1vsn6I0fwzz8mSoIEUqUkswUPlIm-BgDNI_NEFwta1A9XYM55d3fj3hMePj3GciPQNQ7-FP1v8I7PdO97w</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2611585971</pqid></control><display><type>article</type><title>Genetic Correlation Analysis and Transcriptome-wide Association Study Suggest the Overlapped Genetic Mechanism between Gout and Attention-deficit Hyperactivity Disorder</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>SAGE Journals</source><creator>Kafle, Om Prakash ; Wang, Xi ; Cheng, Shiqiang ; Ding, Miao ; Li, Ping ; Cheng, Bolun ; Liang, Xiao ; Liu, Li ; Du, Yanan ; Ma, Mei ; Zhang, Lu ; Zhao, Yan ; Wen, Yan ; Zhang, Feng</creator><creatorcontrib>Kafle, Om Prakash ; Wang, Xi ; Cheng, Shiqiang ; Ding, Miao ; Li, Ping ; Cheng, Bolun ; Liang, Xiao ; Liu, Li ; Du, Yanan ; Ma, Mei ; Zhang, Lu ; Zhao, Yan ; Wen, Yan ; Zhang, Feng</creatorcontrib><description>Objectives:
Gout is a common inflammatory arthritis, which is caused by hyperuricemia. Limited efforts have been paid to systematically explore the relationships between gout and common psychiatric disorders.
Methods:
Genome-wide association study summary data of gout were obtained from the GeneATLAS, which contained 452,264 participants including 3,528 gout cases. Linkage disequilibrium score regression (LDSC) was first conducted to evaluate the genetic relationships between gout and 5 common psychiatric disorders. Transcriptome-wide association studies (TWAS) was then conducted to explore the potential biological mechanism underlying the observed genetic correlation between gout and attention-deficit hyperactivity disorder (ADHD). The Database for Annotation, Visualization and Integrated Discovery online functional annotation system was applied for pathway enrichment analysis and gene ontology enrichment analysis.
Results:
LDSC analysis observed significant genetic correlation between gout and ADHD (genetic correlation coefficients = 0.29, standard error = 0.09 and P value = 0.0015). Further TWAS of gout identified 105 genes with P value < 0.05 in muscle skeleton and 228 genes with P value < 0.05 in blood. TWAS of ADHD also detected 300 genes with P value < 0.05 in blood. Further comparing the TWAS results identified 9 common candidate genes shared by gout and ADHD, such as CD300C (P
gout = 0.0040; P
ADHD = 0.0226), KDM6B (P
gout = 0.0074; P
ADHD = 0.0460), and BST1 (P
gout = 0.0349; P
ADHD = 0.03560).
Conclusion:
We observed genetic correlation between gout and ADHD and identified multiple candidate genes for gout and ADHD.</description><identifier>ISSN: 0706-7437</identifier><identifier>EISSN: 1497-0015</identifier><identifier>DOI: 10.1177/0706743720970844</identifier><identifier>PMID: 33155823</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>ADP-ribosyl Cyclase ; Antigens, CD ; Antigens, Surface ; Attention Deficit Disorder with Hyperactivity - epidemiology ; Attention Deficit Disorder with Hyperactivity - genetics ; Attention deficit hyperactivity disorder ; Correlation analysis ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Gout - epidemiology ; Gout - genetics ; GPI-Linked Proteins ; Humans ; Jumonji Domain-Containing Histone Demethylases ; Membrane Glycoproteins ; Mental disorders ; Original Research ; Transcriptome</subject><ispartof>Canadian journal of psychiatry, 2021-12, Vol.66 (12), p.1077-1084</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020 2020 Canadian Psychiatric Association</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3774-d6672fa7a7edab56735ccbf2464782aa8892534d2875c778b30c753d4693b4683</citedby><cites>FETCH-LOGICAL-c3774-d6672fa7a7edab56735ccbf2464782aa8892534d2875c778b30c753d4693b4683</cites><orcidid>0000-0001-9594-8782</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8689453/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8689453/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,21798,27901,27902,43597,43598,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33155823$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kafle, Om Prakash</creatorcontrib><creatorcontrib>Wang, Xi</creatorcontrib><creatorcontrib>Cheng, Shiqiang</creatorcontrib><creatorcontrib>Ding, Miao</creatorcontrib><creatorcontrib>Li, Ping</creatorcontrib><creatorcontrib>Cheng, Bolun</creatorcontrib><creatorcontrib>Liang, Xiao</creatorcontrib><creatorcontrib>Liu, Li</creatorcontrib><creatorcontrib>Du, Yanan</creatorcontrib><creatorcontrib>Ma, Mei</creatorcontrib><creatorcontrib>Zhang, Lu</creatorcontrib><creatorcontrib>Zhao, Yan</creatorcontrib><creatorcontrib>Wen, Yan</creatorcontrib><creatorcontrib>Zhang, Feng</creatorcontrib><title>Genetic Correlation Analysis and Transcriptome-wide Association Study Suggest the Overlapped Genetic Mechanism between Gout and Attention-deficit Hyperactivity Disorder</title><title>Canadian journal of psychiatry</title><addtitle>Can J Psychiatry</addtitle><description>Objectives:
Gout is a common inflammatory arthritis, which is caused by hyperuricemia. Limited efforts have been paid to systematically explore the relationships between gout and common psychiatric disorders.
Methods:
Genome-wide association study summary data of gout were obtained from the GeneATLAS, which contained 452,264 participants including 3,528 gout cases. Linkage disequilibrium score regression (LDSC) was first conducted to evaluate the genetic relationships between gout and 5 common psychiatric disorders. Transcriptome-wide association studies (TWAS) was then conducted to explore the potential biological mechanism underlying the observed genetic correlation between gout and attention-deficit hyperactivity disorder (ADHD). The Database for Annotation, Visualization and Integrated Discovery online functional annotation system was applied for pathway enrichment analysis and gene ontology enrichment analysis.
Results:
LDSC analysis observed significant genetic correlation between gout and ADHD (genetic correlation coefficients = 0.29, standard error = 0.09 and P value = 0.0015). Further TWAS of gout identified 105 genes with P value < 0.05 in muscle skeleton and 228 genes with P value < 0.05 in blood. TWAS of ADHD also detected 300 genes with P value < 0.05 in blood. Further comparing the TWAS results identified 9 common candidate genes shared by gout and ADHD, such as CD300C (P
gout = 0.0040; P
ADHD = 0.0226), KDM6B (P
gout = 0.0074; P
ADHD = 0.0460), and BST1 (P
gout = 0.0349; P
ADHD = 0.03560).
Conclusion:
We observed genetic correlation between gout and ADHD and identified multiple candidate genes for gout and ADHD.</description><subject>ADP-ribosyl Cyclase</subject><subject>Antigens, CD</subject><subject>Antigens, Surface</subject><subject>Attention Deficit Disorder with Hyperactivity - epidemiology</subject><subject>Attention Deficit Disorder with Hyperactivity - genetics</subject><subject>Attention deficit hyperactivity disorder</subject><subject>Correlation analysis</subject><subject>Genetic Predisposition to Disease</subject><subject>Genome-Wide Association Study</subject><subject>Gout - epidemiology</subject><subject>Gout - genetics</subject><subject>GPI-Linked Proteins</subject><subject>Humans</subject><subject>Jumonji Domain-Containing Histone Demethylases</subject><subject>Membrane Glycoproteins</subject><subject>Mental disorders</subject><subject>Original Research</subject><subject>Transcriptome</subject><issn>0706-7437</issn><issn>1497-0015</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kk1v1DAQQCMEokvhzglZ4sIl4M_YuSCtFrpFKuqh5Rw59mTXVRIH29kq_4if2YRtC1TCFx_mzZvxeLLsLcEfCZHyE5a4kJxJikuJFefPshXhpcwxJuJ5tlrC-RI_yV7FeIPnQ6l6mZ0wRoRQlK2yX1voITmDNj4EaHVyvkfrXrdTdBHp3qLroPtoghuS7yC_dRbQOkZv3JG9SqOd0NW420FMKO0BXR4gtHoYwKIH-Xcwe9272KEa0i1Aj7Z-TL_165SgX0y5hcYZl9D5NEDQJrmDSxP64qIPFsLr7EWj2whv7u_T7MfZ1-vNeX5xuf22WV_khknJc1sUkjZaaglW16KQTBhTN5QXXCqqtVIlFYxbqqQwUqqaYSMFs7woWc0LxU6zz0fvMNYdWDM3F3RbDcF1OkyV1676N9K7fbXzh0oVquSCzYIP94Lgf47zUKrORQNtq3vwY6woFwqzQvGl1vsn6I0fwzz8mSoIEUqUkswUPlIm-BgDNI_NEFwta1A9XYM55d3fj3hMePj3GciPQNQ7-FP1v8I7PdO97w</recordid><startdate>20211201</startdate><enddate>20211201</enddate><creator>Kafle, Om Prakash</creator><creator>Wang, Xi</creator><creator>Cheng, Shiqiang</creator><creator>Ding, Miao</creator><creator>Li, Ping</creator><creator>Cheng, Bolun</creator><creator>Liang, Xiao</creator><creator>Liu, Li</creator><creator>Du, Yanan</creator><creator>Ma, Mei</creator><creator>Zhang, Lu</creator><creator>Zhao, Yan</creator><creator>Wen, Yan</creator><creator>Zhang, Feng</creator><general>SAGE Publications</general><general>SAGE PUBLICATIONS, INC</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>4T-</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9594-8782</orcidid></search><sort><creationdate>20211201</creationdate><title>Genetic Correlation Analysis and Transcriptome-wide Association Study Suggest the Overlapped Genetic Mechanism between Gout and Attention-deficit Hyperactivity Disorder</title><author>Kafle, Om Prakash ; Wang, Xi ; Cheng, Shiqiang ; Ding, Miao ; Li, Ping ; Cheng, Bolun ; Liang, Xiao ; Liu, Li ; Du, Yanan ; Ma, Mei ; Zhang, Lu ; Zhao, Yan ; Wen, Yan ; Zhang, Feng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3774-d6672fa7a7edab56735ccbf2464782aa8892534d2875c778b30c753d4693b4683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>ADP-ribosyl Cyclase</topic><topic>Antigens, CD</topic><topic>Antigens, Surface</topic><topic>Attention Deficit Disorder with Hyperactivity - epidemiology</topic><topic>Attention Deficit Disorder with Hyperactivity - genetics</topic><topic>Attention deficit hyperactivity disorder</topic><topic>Correlation analysis</topic><topic>Genetic Predisposition to Disease</topic><topic>Genome-Wide Association Study</topic><topic>Gout - epidemiology</topic><topic>Gout - genetics</topic><topic>GPI-Linked Proteins</topic><topic>Humans</topic><topic>Jumonji Domain-Containing Histone Demethylases</topic><topic>Membrane Glycoproteins</topic><topic>Mental disorders</topic><topic>Original Research</topic><topic>Transcriptome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kafle, Om Prakash</creatorcontrib><creatorcontrib>Wang, Xi</creatorcontrib><creatorcontrib>Cheng, Shiqiang</creatorcontrib><creatorcontrib>Ding, Miao</creatorcontrib><creatorcontrib>Li, Ping</creatorcontrib><creatorcontrib>Cheng, Bolun</creatorcontrib><creatorcontrib>Liang, Xiao</creatorcontrib><creatorcontrib>Liu, Li</creatorcontrib><creatorcontrib>Du, Yanan</creatorcontrib><creatorcontrib>Ma, Mei</creatorcontrib><creatorcontrib>Zhang, Lu</creatorcontrib><creatorcontrib>Zhao, Yan</creatorcontrib><creatorcontrib>Wen, Yan</creatorcontrib><creatorcontrib>Zhang, Feng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Docstoc</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Canadian journal of psychiatry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kafle, Om Prakash</au><au>Wang, Xi</au><au>Cheng, Shiqiang</au><au>Ding, Miao</au><au>Li, Ping</au><au>Cheng, Bolun</au><au>Liang, Xiao</au><au>Liu, Li</au><au>Du, Yanan</au><au>Ma, Mei</au><au>Zhang, Lu</au><au>Zhao, Yan</au><au>Wen, Yan</au><au>Zhang, Feng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic Correlation Analysis and Transcriptome-wide Association Study Suggest the Overlapped Genetic Mechanism between Gout and Attention-deficit Hyperactivity Disorder</atitle><jtitle>Canadian journal of psychiatry</jtitle><addtitle>Can J Psychiatry</addtitle><date>2021-12-01</date><risdate>2021</risdate><volume>66</volume><issue>12</issue><spage>1077</spage><epage>1084</epage><pages>1077-1084</pages><issn>0706-7437</issn><eissn>1497-0015</eissn><abstract>Objectives:
Gout is a common inflammatory arthritis, which is caused by hyperuricemia. Limited efforts have been paid to systematically explore the relationships between gout and common psychiatric disorders.
Methods:
Genome-wide association study summary data of gout were obtained from the GeneATLAS, which contained 452,264 participants including 3,528 gout cases. Linkage disequilibrium score regression (LDSC) was first conducted to evaluate the genetic relationships between gout and 5 common psychiatric disorders. Transcriptome-wide association studies (TWAS) was then conducted to explore the potential biological mechanism underlying the observed genetic correlation between gout and attention-deficit hyperactivity disorder (ADHD). The Database for Annotation, Visualization and Integrated Discovery online functional annotation system was applied for pathway enrichment analysis and gene ontology enrichment analysis.
Results:
LDSC analysis observed significant genetic correlation between gout and ADHD (genetic correlation coefficients = 0.29, standard error = 0.09 and P value = 0.0015). Further TWAS of gout identified 105 genes with P value < 0.05 in muscle skeleton and 228 genes with P value < 0.05 in blood. TWAS of ADHD also detected 300 genes with P value < 0.05 in blood. Further comparing the TWAS results identified 9 common candidate genes shared by gout and ADHD, such as CD300C (P
gout = 0.0040; P
ADHD = 0.0226), KDM6B (P
gout = 0.0074; P
ADHD = 0.0460), and BST1 (P
gout = 0.0349; P
ADHD = 0.03560).
Conclusion:
We observed genetic correlation between gout and ADHD and identified multiple candidate genes for gout and ADHD.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>33155823</pmid><doi>10.1177/0706743720970844</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0001-9594-8782</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central; SAGE Journals |
| subjects | ADP-ribosyl Cyclase Antigens, CD Antigens, Surface Attention Deficit Disorder with Hyperactivity - epidemiology Attention Deficit Disorder with Hyperactivity - genetics Attention deficit hyperactivity disorder Correlation analysis Genetic Predisposition to Disease Genome-Wide Association Study Gout - epidemiology Gout - genetics GPI-Linked Proteins Humans Jumonji Domain-Containing Histone Demethylases Membrane Glycoproteins Mental disorders Original Research Transcriptome |
| title | Genetic Correlation Analysis and Transcriptome-wide Association Study Suggest the Overlapped Genetic Mechanism between Gout and Attention-deficit Hyperactivity Disorder |
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