Identification of Novel Alzheimer’s Disease Loci Using Sex-Specific Family-Based Association Analysis of Whole-Genome Sequence Data

Cohort description and sequencing

Briefly, sequencing in NIMH was performed by Illumina HiSeq 2000. Alignment to the human reference genome (GRh37) was done with bwa-mem⁵⁰ (v0.7.7, default parameters). Variants were jointly called for each family using FreeBayes⁵¹ (v0.9.9.2-18) and GATK⁵² (v3.0) best practices method as part of the bcbio-nextgen workflow⁵³ before being squared-off with bcbio.recall across the whole cohort to distinguish reference calls from no variant calls. Library and read quality were assessed using FastQC⁵⁴ (v0.10.1) and Qualimap⁵⁵ (v0.7.1). Variant calls in vcf format for the families from the NIA ADSP cohort were obtained from the National Institute on Aging Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS) under accession number: NG00067 and the database of Genotypes and Phenotypes (dbGaP) under accession number: phs000572v8p4. Both cohorts: NIMH³²…