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Here we show that a key \u03b15 gene variant Asp398Asn is associated with a dorsal anterior cingulate\u2013ventral striatum\/extended amygdala circuit, such that the \u201crisk allele\u201d decreases the intrinsic resting functional connectivity strength in this circuit. Importantly, this effect is observed independently in nonsmokers and smokers, although the circuit strength distinguishes smokers from nonsmokers, predicts addiction severity in smokers, and is not secondary to smoking per se, thus representing a trait-like circuitry biomarker. This same circuit is further impaired in people with mental illnesses, who have the highest rate of smoking. Identifying where and how brain circuits link genes to smoking provides practical neural circuitry targets for new treatment development.<\/jats:p>","DOI":"10.1073\/pnas.1004745107","type":"journal-article","created":{"date-parts":[[2010,7,20]],"date-time":"2010-07-20T00:50:30Z","timestamp":1279587030000},"page":"13509-13514","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":153,"title":["A genetically modulated, intrinsic cingulate circuit supports human nicotine addiction"],"prefix":"10.1073","volume":"107","author":[{"given":"L. 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