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[<jats:sup>18<\/jats:sup>F]altanserin and [<jats:sup>11<\/jats:sup>C]Cimbi\u201036 positron emission tomography (PET) allow for high\u2010resolution imaging of 5\u2010HT2AR in the living human brain. Cerebral 5\u2010HT2AR binding is strongly genetically determined, though the impact of specific variants is poorly understood. Candidate gene studies suggest that <jats:italic>HTR2A<\/jats:italic> single nucleotide polymorphisms including rs6311\/rs6313, rs6314, and rs7997012 may influence risk for psychiatric disorders and mediate treatment response. Although known to impact in vitro expression of 5\u2010HT2AR or other serotonin (5\u2010HT) proteins, their effect on human in vivo brain 5\u2010HT2AR binding has as of yet been insufficiently studied. We thus assessed the extent to which these variants and the commonly studied 5\u2010HTTLPR predict neocortex in vivo 5\u2010HT2AR binding in healthy adult humans. We used linear regression analyses and likelihood ratio tests in 197 subjects scanned with [<jats:sup>18<\/jats:sup>F]altanserin or [<jats:sup>11<\/jats:sup>C]Cimbi\u201036 PET. Although we observed genotype group differences in 5\u2010HT2AR binding of up to ~10%, no genetic variants were statistically significantly predictive of 5\u2010HT2AR binding in what is the largest human in vivo 5\u2010HT2AR imaging genetics study to date. Thus, in vitro and post mortem results suggesting effects on 5\u2010HT2AR expression did not carry over to the in vivo setting. To any extent these variants might affect clinical risk, our findings do not support that 5\u2010HT2AR binding mediates such effects. Our observations indicate that these individual variants do not significantly contribute to genetic load on human in vivo 5\u2010HT2AR binding.<\/jats:p>","DOI":"10.1002\/hbm.25138","type":"journal-article","created":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T15:38:38Z","timestamp":1595432318000},"page":"4518-4528","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Common <scp><i>HTR2A<\/i><\/scp> variants and <scp>5\u2010HTTLPR<\/scp> are not associated with human in vivo serotonin <scp>2A<\/scp> receptor levels"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9963-9044","authenticated-orcid":false,"given":"Marie","family":"Spies","sequence":"first","affiliation":[{"name":"Neurobiology Research Unit, Rigshospitalet  Copenhagen Denmark"},{"name":"Department of Psychiatry and Psychotherapy Medical University of Vienna  Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arafat","family":"Nasser","sequence":"additional","affiliation":[{"name":"Neurobiology Research Unit, Rigshospitalet  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brice","family":"Ozenne","sequence":"additional","affiliation":[{"name":"Neurobiology Research Unit, Rigshospitalet  Copenhagen Denmark"},{"name":"Department of Public Health, Section of Biostatistics University of Copenhagen  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter S.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Neurobiology Research Unit, Rigshospitalet  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gitte M.","family":"Knudsen","sequence":"additional","affiliation":[{"name":"Neurobiology Research Unit, Rigshospitalet  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick M.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Neurobiology Research Unit, Rigshospitalet  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,7,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145705005055"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2003.10.046"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-244X-7-22"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)92168-0"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4000348"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2012.09.006"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2013.1378"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2016.12.030"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001366"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1083968"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-009-1538-z"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000087847"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1159\/000075337"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19990628)409:2<187::AID-CNE2>3.0.CO;2-P"},{"key":"e_1_2_8_16_1","first-page":"679","volume-title":"The use of psychological testing for treatment planning and outcomes assessment","author":"Derogatis L. 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