Atrial fibrillation (AF) is the most common type of cardiac arrhythmia affecting about 1% of the general population, and the incidence increases strongly with age. A number of diseases such as hypertension, ischemic heart disease and metabolic diseases predispose to AF, and patients devoid of confounding diseases are said to have lone AF. We assume that genetic factors may be specifically important in young AF patients and investigated a cohort of 197 patients developing lone AF before the age of 40. The average age of onset was 31 years. In this young lone AF cohort, 10 variants of Nav1.5 were found distributed widely over the length of the protein. Nine out of 10 variants had compromised peak current, and 5 out of 5 that were studied for effects on the sustained Na current had a 3-8 fold increase. Interestingly, 7 of the probands carried a mutation previously associated with Long QT syndrome type 3, and these were also the patients showing the longest QT intervals in our study. The overlap between the diseases could indicate an increased tendency to early afterdepolarization in both atria and ventricles. The young patients further showed a number of mutations in Kv7.1 conducting the cardiac Iks current and in Kv1.5 conducting the atrial Ikur current. In Kv7.1 four mutations were found (3 gain- and 1 loss-of-function), and in Kv1.5 six mutations were detected (3 gain- and 3 loss-of-function). Gain-of-function mutations in Kv1.5 have not been described before as cause of AF. The Kv1.5 loss-of-function variants were caused by decreased surface expression. None of the above variants were present in 307 healthy control individuals. In conclusion, patients with the onset of AF at young age exhibit a high prevalence of Nav and Kv variants. The Nav variants are dominated by a decreased peak current and an increases late current, whereas both loss- and gain-of-function of the Kv channels are seen to enhance AF susceptibility.