Some researchers have hypothesized that there may be large panels of rare functional variants, each of large effect, that predict risk for alcoholism with different variants occurring in different people. It is becoming increasingly easy, and the costs are rapidly decreasing, to detect rare variants using next-generation sequencing. Sequencing is rapidly becoming the key tool for characterization of the genetic basis of human diseases [84]. Clearly very large sample sizes are required to detect large panels of rare variants and there are significant bioinformatic requirements to deal with vast quantities of data. One such successful study performed exon-focused sequencing of impulsive individuals derived from a Finnish population isolate and identified a stop codon in HTR2B (1% frequency) that was unique to Finns. The stop codon carriers performed violently impulsive acts, but only whilst intoxicated with alcohol [85].
