Computational protocol: A sex-specific association of common variants of neuroligin genes (NLGN3 and NLGN4X) with autism spectrum disorders in a Chinese Han cohort

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Protocol publication

[…] Considering highly varying prevalence in female and male patients of ASDs, we separate subjects by gender into case and control subgroups. The Hardy-Weinberg equilibrium (HWE) for SNP markers on the X chromosome can be examined by testing two null hypotheses: H1: allele frequencies between males and females are equal and H2: HWE holds in females[]. A basic association of allele frequencies was analyzed in PLINK version 1.07 software (http://pngu.mgh.harvard.edu/purcell/plink/; Purcell et al, 2009)[] and corrected by Bonferroni's approach for multiple testing as the most stringent test to control false-positive results. The crude odds ratios (ORs) with 95% confidence intervals (95% CIs) were estimated for the effects of high-frequency allele in the case group. Pair-wise linkage disequilibrium (LD) between the different markers was estimated by the D' and r2, using Haploview version 4.2 software (http://www.broad.mit.edu/mpg/haploview Barrett et al., 2005)[] with visualized structure. Haplotype blocks within each gene were defined by the default algorithm of Gabriel method[] and haplotype frequencies were estimated with the expectation maximization (EM) algorithm, excluding haplotypes with frequencies lower than 5%. While for X-linked SNP in male samples, genotype of each SNP was interpreted as homozygous (genotype XAXA or XBXB), although the male X was hemizygous (genotype XA or XB). The exact P-values with 10,000 permutations were done for multiple test correction of the observed haplotype association. The differences were considered statistically significant with P < 0.05. Post-hoc power analysis was implemented using the computer G*Power.SNPs were removed from analysis if they had the percentage of non-missing genotypes less than 0.95, displayed Hardy-Weinberg disequilibrium (P < 0.05), or had a minor allele frequency (MAF) < 0.05. […]

Pipeline specifications

Software tools PLINK, Haploview, G*Power
Applications Miscellaneous, GWAS
Organisms Homo sapiens