{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:16:31Z","timestamp":1791926191094,"version":"4.3.4"},"reference-count":72,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Existing observational studies examining the effect of body fat on the risk of Parkinson disease (PD) have yielded inconsistent results. We aimed to investigate this causal relationship at the genetic level.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We employed two\u2010sample Mendelian randomization (TSMR) to investigate the causal effects of body fat on PD, with multiple sex\u2010specific body fat measures being involved. We performed Bayesian colocalization analysis and cross\u2010trait meta\u2010analysis to reveal pleiotropic genomic loci shared between body mass index (BMI) and PD. Finally, we used the MAGMA tool to perform tissue enrichment analysis of the genome\u2010wide association study hits of BMI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TSMR analysis suggests that except waist circumference, higher measures of body fatness are associated with a decreased risk of PD, including BMI (OR: 0.83), body fat percentage (OR: 0.69), body fat mass (OR: 0.77), and hip circumference (OR: 0.83). The observed effects were slightly more pronounced in females than males. Colocalization analysis highlighted two colocalized regions (chromosome 3p25.3 and chromosome 17p12) shared by BMI and PD and pointed to some genes as possible players, including\n                      <jats:italic>SRGAP3<\/jats:italic>\n                      ,\n                      <jats:italic>MTMR14<\/jats:italic>\n                      , and\n                      <jats:italic>ADORA2B<\/jats:italic>\n                      . Cross\u2010trait meta\u2010analysis successfully identified 10 novel genomic loci, involving genes of\n                      <jats:italic>TOX3<\/jats:italic>\n                      and\n                      <jats:italic>MAP4K4<\/jats:italic>\n                      . Tissue enrichment analysis showed that BMI\u2010associated genetic variants were enriched in multiple brain tissues.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We found that nonabdominal body fatness exerts a robust protective effect against PD. Our colocalization analysis and cross\u2010trait meta\u2010analysis identified pleiotropic genetic variation shared between BMI and PD, providing new clues for understanding the association between body fat and PD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70132","type":"journal-article","created":{"date-parts":[[2024,11,23]],"date-time":"2024-11-23T02:44:07Z","timestamp":1732329847000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Novel Insights Into the Causal Effects and Shared Genetics Between Body Fat and Parkinson Disease"],"prefix":"10.1111","volume":"30","author":[{"given":"Qian","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Psychiatry The Affiliated Brain Hospital of Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongming","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiology Affiliated Drum Tower Hospital, Medical School of Nanjing University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ancha","family":"Baranova","sequence":"additional","affiliation":[{"name":"School of Systems Biology George Mason University  Manassas Virginia USA"},{"name":"Research Centre for Medical Genetics  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbao","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Systems Biology George Mason University  Manassas Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3204-8191","authenticated-orcid":false,"given":"Fuquan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry The Affiliated Brain Hospital of Nanjing Medical University  Nanjing Jiangsu China"},{"name":"Institute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/advances\/nmy055"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1037\/0022-006X.70.3.510"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-018-1107-0"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(17)30200-0"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/53.6.1561S"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2008.05.003"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)70807-2"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14158"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.55.9.1358"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2012.07.026"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1592\/phco.27.12part2.155S"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes12071006"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-022-00353-4"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.2005.00571.x"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000201468"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2014.168"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/13557858.2018.1469737"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002314"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000209620"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8060259"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2020.06.015"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28536"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30320-5"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35553-2"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu328"},{"issue":"4","key":"e_1_2_10_27_1","first-page":"547","article-title":"Mendelian Randomization Approach, Used for Causal Inferences","volume":"38","author":"Wang L. N.","year":"2017","journal-title":"Zhonghua Liu Xing Bing Xue Za Zhi = Zhonghua Liuxingbingxue Zazhi"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004383"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.11.011"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv080"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyy258"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008720"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7274-6_22"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01261-5"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004219"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2653"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1515\/revneuro-2022-0093"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002640"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2015.00155"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8101207"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-023-01734-1"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddac230"},{"key":"e_1_2_10_44_1","first-page":"1","article-title":"DNA Methylation Mediated the Association of Body Mass Index With Blood Pressure in Chinese Monozygotic Twins","volume":"27","author":"Yao J.","year":"2024","journal-title":"Twin Research and Human Genetics: The Official Journal of the International Society for Twin Studies"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.2337\/db10-1070"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep42014"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13105-016-0520-6"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2014.02.005"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes10110945"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21780"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-015-1018-2"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0805555106"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-021-02343-x"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.01.019"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.2337\/db08-1770"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.2114\/jpa2.26.109"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.732"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2021.11.011"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-191683"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14149"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2007.04616.x"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23388"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pjnns.2014.08.004"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1550-8579(07)80003-9"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-01474"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10028"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000046523.05125.87"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.1052"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41366-023-01371-9"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12603-022-1736-5"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanwpc.2023.100877"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina59020309"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1186\/1743-7075-6-7"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.70132","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T11:34:04Z","timestamp":1744803244000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cns.70132"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11]]},"references-count":72,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1111\/cns.70132"],"URL":"https:\/\/doi.org\/10.1111\/cns.70132","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11]]},"assertion":[{"value":"2024-08-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70132"}}