Affective disorders constitute major health problems with marked heritability. We aim to identify gene variants underlying susceptibility to bipolar disorder, seasonal affective disorder and various pain conditions. Large patient collections were created by use of Swedish registries and the public health care systems. Specifically we study polymorphisms and DNA sequence of gene pathways involved in transmitter, neuroendocrine, stress and circadian regulation in over 1000 bipolar subjects and controls,, 300 SAD patients, and over 2000 pain patients. A particular aim is to correlate endophenotypes, or specific components of these disorders to variantions in biochemical pathways. We also study genetic/epigenetic changes in samples above and correlate to symptoms, treatment response, lifestyle factors and disease. Another important aspect is to determine changes in expression of vulnerability genes using DNA arrays, and correlate with variation in phenotype. We are part of international consortia that analyze bipolar next-gen sequencing and genome wide association data, in particular related to drug response. The significance of gene identification can hardly be overestimated. It will lead to an understanding of casual pathways. Specific variants will be used for predicting treatment outcome, as well as side effects. This will permit individualized treatment strategies and enable early intervention strategies.