Association analysis was carried out using a likelihood procedure described in a previous publication implemented in NEMO software26. Allele-specific ORs and associated P values were calculated assuming a multiplicative model for the two chromosomes of an individual. Association was tested using a standard likelihood ratio statistic that, if the subjects were unrelated, would have asymptotically a chi-squared distribution with 1 degree of freedom under the null hypothesis. To correct for relatedness and potential population stratification in the genome-wide typed samples (SGENE-plus and follow-up set 1), genomic control was used27. Inflation factors, estimated by dividing the median of the 314,868 chi-squared statistics by 0.6752, were 1.01, 1.03, 1.09, 1.05, 1.05, 1.19, 1.04 and 1.09 for the SGENE-plus England, Finland (Helsinki), Finland (Kuusamo), Germany (Bonn), Germany (Munich), Iceland, Italy and Scotland groups, respectively, and 1.08 for follow-up set 1. The inflation factor was large in Iceland because of the inclusion of close relatives in that data set. Both SGENE-plus and the follow-up samples were combined using the Mantel–Haenszel model28.
