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Chunk #9 — Methods and Materials — Testing the Female Protective Effect Hypothesis

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A Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder.
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A leave-one-study/wave-out approach was used to maximize power and maintain independent target and discovery samples for PRS analyses using the standard approach 39, 40. GWAS results from 23andMe were also included in discovery meta-analyses. A PRS was calculated for each individual in each target sample (European-only samples) by scoring the number of alleles weighted by log(odds ratio [OR]) across the set of clumped, meta-analyzed SNPs in PLINK version 1.9 (see Supplemental Table S2). PRSs were standardized using z-score transformations; ORs can be interpreted as increase in risk of the outcome per standard deviation in PRS. Logistic regression analyses including principal components were used to test for association of PRS with sex in cases (female individuals were coded as 1). Results of these leave-one-study/wave-out analyses were meta-analyzed.