{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:40:55Z","timestamp":1787499655105,"version":"build-2736575974"},"reference-count":136,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,8]],"date-time":"2025-03-08T00:00:00Z","timestamp":1741392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Neurological Disorders and Stroke","award":["NS19788"],"award-info":[{"award-number":["NS19788"]}]},{"name":"National Institute of Neurological Disorders and Stroke","award":["R01 AA11031"],"award-info":[{"award-number":["R01 AA11031"]}]},{"name":"National Institute of Neurological Disorders and Stroke","award":["DAMD 17-00-1-0578"],"award-info":[{"award-number":["DAMD 17-00-1-0578"]}]},{"name":"National Institute on Alcohol Abuse and Alcoholism","award":["NS19788"],"award-info":[{"award-number":["NS19788"]}]},{"name":"National Institute on Alcohol Abuse and Alcoholism","award":["R01 AA11031"],"award-info":[{"award-number":["R01 AA11031"]}]},{"name":"National Institute on Alcohol Abuse and Alcoholism","award":["DAMD 17-00-1-0578"],"award-info":[{"award-number":["DAMD 17-00-1-0578"]}]},{"name":"United States Department of Defense","award":["NS19788"],"award-info":[{"award-number":["NS19788"]}]},{"name":"United States Department of Defense","award":["R01 AA11031"],"award-info":[{"award-number":["R01 AA11031"]}]},{"name":"United States Department of Defense","award":["DAMD 17-00-1-0578"],"award-info":[{"award-number":["DAMD 17-00-1-0578"]}]},{"name":"New York State OMH NKI 2023","award":["NS19788"],"award-info":[{"award-number":["NS19788"]}]},{"name":"New York State OMH NKI 2023","award":["R01 AA11031"],"award-info":[{"award-number":["R01 AA11031"]}]},{"name":"New York State OMH NKI 2023","award":["DAMD 17-00-1-0578"],"award-info":[{"award-number":["DAMD 17-00-1-0578"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Natural gene variants of metabotropic glutamate receptor subtype 7 (Grm7), coding for mGluR7, affect individuals\u2019 alcohol-drinking preference. Psychopharmacological investigations have suggested that mGluR7 is also involved in responses to cocaine, morphine, and nicotine exposures. We review the pleiotropic effects of Grm7 and the principle of recombinant quantitative trait locus introgression (RQI), which led to the discovery of the first mammalian quantitative gene accounting for alcohol-drinking preference. Grm7\/GRM7 can play important roles in mammalian ontogenesis, brain development, and predisposition to addiction. It is also involved in other behavioral phenotypes, including emotion, stress, motivated cognition, defensive behavior, and pain-related symptoms. This review identified pleiotropy and the modulation of neurobehavioral processes by variations in the gene Grm7\/GRM7. Patterns of pleiotropic genes can form oligogenic architectures whosecombined additive and interaction effects can significantly predispose individuals to the expressions of disorders. Identifying and characterizing pleiotropic genes are necessary for understanding the expressions of complex traits. This requires tasks, such as discovering and identifying novel genetic elements of the genetic architecture, which are unsuitable for AI but require classical experimental genetics.<\/jats:p>","DOI":"10.3390\/biom15030392","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T08:46:41Z","timestamp":1741596401000},"page":"392","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Pleiotropic Effects of Grm7\/GRM7 in Shaping Neurodevelopmental Pathways and the Neural Substrate of Complex Behaviors and Disorders"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4948-4970","authenticated-orcid":false,"given":"Beatrix M.","family":"Gyetvai","sequence":"first","affiliation":[{"name":"Laboratory of Neurobehavior Genetics, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd., Orangeburg, NY 10962, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Csaba","family":"Vadasz","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobehavior Genetics, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd., Orangeburg, NY 10962, USA"},{"name":"Department of Psychiatry, New York University Langone Medical Center, New York, NY 10016, USA"},{"name":"Kalymma, Stony Point, New York, NY 10980, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,8]]},"reference":[{"key":"ref_1","first-page":"399","article-title":"The correlation between relatives on the supposition of mendelian inheritance","volume":"53","author":"Fisher","year":"1918","journal-title":"Trans. R. Soc. Edinb."},{"key":"ref_2","unstructured":"Wright, S. (1984). 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