Substance use is notoriously difficult to treat. Treatment strategies have tended to focus on replacement (as for nicotine and opioid replacement) and abstinence, sometimes together with self-help groups or psychotherapy1–3. To provide better treatments, we require better understanding of the underlying biology. SUDs have long been known to be moderately heritable. In particular, genetic influences on SUD traits were shown decades ago via genetic epidemiology methods: twin and adoption studies4. This research was critical in establishing a basis for gene mapping in SUDs, but the twin-study framework was well established a decade ago and has advanced little relative to molecular gene mapping successes. Genetic studies have been considered a key tool for identifying targets to develop more effective treatments. However, we are just starting to comprehend and dissect the highly polygenic architecture of these complex traits. The main steps forward in this field have occurred recently and over just a few years. This is attributable to the advent of large biobanks and consortia that are allowing study of sample sizes that until recently were unimaginable.
