GWAS summary statistics for clinically diagnosed AD86 (link), PD87 (link), FTD88 , CBD89 (link) and PSP20 (link) in individuals of European ancestry were obtained. For AD, we used the clinical diagnosis as the case definition to avoid spurious genetic correlations that could have been introduced through the by-proxy design31 (link), in which by-proxy cases are defined as having a parent with AD. Although this is a powerful design for gene discovery and the genetic correlation with clinically diagnosed AD is high90 (link), mislabeling by-proxy cases when parents suffer from other types of dementia (for example, Lewy body dementia, Parkinson’s dementia, FTD or vascular dementia) can lead to spurious genetic correlations with ALS and other neurodegenerative diseases. For FTD, we primarily used the results of the cross-subtype meta-analysis, which includes behavioral variant FTD, semantic dementia FTD, progressive non-fluent aphasia FTD and mndFTD. For CBD, allele coding was unavailable, and effect alleles were inferred by matching allele frequencies to those observed in the Haplotype Reference Consortium. SNPs with MAF > 0.4 were excluded. Because downstream methods rely on LD scores or population-specific LD patterns, the European ancestry summary statistics from the present study were used for ALS. For sample size parameters, effective sample size was calculated as described previously.
Multiple sclerosis summary statistics were obtained from the International Multiple Sclerosis Genetics Consortium91 (link). For cerebrovascular diseases, GWAS summary statistics were obtained for ischemic stroke (any ischemic stroke)92 (link), intracerebral hemorrhage93 (link) and intracranial aneurysm94 (link). For psychiatric traits, GWAS summary statistics were obtained from Psychiatric Genomics Consortium studies on anorexia nervosa95 (link), obsessive–compulsive disorder96 , anxiety disorders (anxiety score)97 (link), post-traumatic stress disorder (all European ancestries)98 (link), major depressive disorder99 (link), bipolar disorder100 (link), schizophrenia101 , Tourette’s syndrome102 (link), autism spectrum disorder103 (link) and attention-deficit hyperactivity disorder (European ancestries)104 (link).
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