DNA was extracted from blood samples. Genotyping of CROATIA-Vis, LBC and English samples was conducted by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Western General Hospital, Scotland. CROATIA-Korcula and ORCADES genotyping was undertaken by Helmholtz Zentrum München, GmbH, Neuherberg, Germany, and the Nijmegen Biomedical Study genotyping was performed by deCODE Genetics, Iceland. For genotype quality control (QC) procedures see Table S1. Standard checks for gender discrepancies, individual relatedness (in the non-isolate cohorts only), and non-Caucasian ascent were done—with necessary exclusions made. Population stratification factors were estimated via multidimensional scaling (MDS) using an identity-by-state distance matrix; the first three MDS components were covaried for in the association analysis.