procedure. Linkage disequilibrium plots were generated using Haploview (Barrett et al., 2005). Haplotype frequency estimation and haplotype-association analysis was performed using PLINK. The possibility of bias due to non-independence within couple pairs was explored using a Generalized Estimating Equation (GEE)(Liang and Zeger, 1986; Zeger and Liang, 1986) analysis as implemented in the GEE library in the R statistical computing language (R Development Core Team, 2008). Plots were generated using R. Functionality of one missense mutation (presented in the footnote to table 1) was examined using Polyphen-2 (http://genetics.bwh.harvard.edu/pph2/) (Adzhubei et al., 2010). All genomic positions are based on the hg19 (February 2009) human genome assembly.
