{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T17:56:03Z","timestamp":1778954163643,"version":"3.51.4"},"reference-count":22,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T00:00:00Z","timestamp":1730160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>\u00a0Background: Substance use disorder in the United States represents a complex and growing public health crisis, marked by increasing rates of overdose deaths and the misuse of prescription medications. There is a critical need for furthering the understanding of the molecular and genetic mechanisms that can lead to substance use disorder. Identifying significant variants in the kynurenine pathway could help identify therapeutic targets for intervention. Methods: The All of Us cohort builder evaluated the frequency of variants of four genes, TDO2, IDO1, IDO2, and KMO, encoding enzymes in the kynurenine pathway. The samples were broken into six cohorts: alcohol, cannabis, cocaine, opioid, other use disorder, and control. Using Chi-square analysis, the frequency of at least one copy of a variant allele was calculated. Results: Chi-square analysis showed a significant variation in genetic frequency (p-value &lt; 0.005) in 14 of 18 polymorphisms analyzed. The cocaine cohort had the most significant variants (13), cannabis had 11, opioids had 3, other use disorders had 2, and alcohol had 1 significant variant. Conclusions: This study found associations of polymorphisms in the TDO2, IDO1, IDO2, and KMO genes of individuals with a substance use disorder. These results provide evidence of potential predictors of increased susceptibility to substance use disorder.\u00a0<\/jats:p>","DOI":"10.3390\/genes15111388","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T04:51:33Z","timestamp":1730177493000},"page":"1388","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Gene Variant Frequencies of IDO1, IDO2, TDO, and KMO in Substance Use Disorder Cohorts"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8549-5299","authenticated-orcid":false,"given":"Lindsey","family":"Contella","sequence":"first","affiliation":[{"name":"Healthcare Genetics and Genomics, School of Nursing, Clemson University, 605 Grove Rd., Greenville, SC 29605, USA"},{"name":"Luxor Scientific, LLC, 1327 Miller Rd., Greenville, SC 29607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3672-3492","authenticated-orcid":false,"given":"Christopher L.","family":"Farrell","sequence":"additional","affiliation":[{"name":"Healthcare Genetics and Genomics, School of Nursing, Clemson University, 605 Grove Rd., Greenville, SC 29605, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2017-4270","authenticated-orcid":false,"given":"Luigi","family":"Boccuto","sequence":"additional","affiliation":[{"name":"Healthcare Genetics and Genomics, School of Nursing, Clemson University, 605 Grove Rd., Greenville, SC 29605, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alain","family":"Litwin","sequence":"additional","affiliation":[{"name":"School of Health Research, Clemson University, Clemson, SC 29631, USA"},{"name":"Department of Medicine, Prisma Health, 701 Grove Rd., Greenville, SC 29605, USA"},{"name":"Department of Medicine, University of South Carolina School of Medicine, 876 W Faris Rd., Greenville, SC 29605, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marion L.","family":"Snyder","sequence":"additional","affiliation":[{"name":"Luxor Scientific, LLC, 1327 Miller Rd., Greenville, SC 29607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11121-023-01503-7","article-title":"Introduction to helping to end addiction long-term prevention cooperative: Overview and strategies","volume":"24","author":"Ridenour","year":"2023","journal-title":"Prev. 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