We next tested for association of rs1685199 with depression in three additional sample sets: a group of individuals referred from primary care to a hospital outpatient clinic (n=467 rMDD patients), and two population-based samples drawn from primary care as part of the Generation Scotland: Scottish Family Health Study consisting of 645 cases with rMDD and 690 cases with single episode MDD. All three groups were compared with 4017 controls drawn exclusively from Generation Scotland: Scottish Family Health Study (Supplementary additional text and Table S4). No significant association was seen with any individual replication set or all three combined (best P=0.088). Analysis of all three rMDD sets, both the original set and the two rMDD replication sets, was supportive of association (1112 rMDD, 4017 controls; P=0.0058, OR=1.46, 95%CI=1.12–1.91). Combined analysis of both sets of individuals referred from primary care showed stronger nominal association (P=0.00065, OR=1.76, 95%CI=1.27–2.44). No association was seen in the combined analysis of both the rMDD and MDD population-based replication sets (P=0.41). The risk allele for rs16856199 did not segregate with rMDD in 10 families of carriers identified from