Exome sequencing and data analysis
Genomic DNA was extracted from peripheral blood leukocytes using DNeasy Blood & Tissue Kit (Qiagen). Exome sequences were captured with SureSelect Target Enrichment System for Illumina Paired-End Sequencing Library (Agilent Technologies), and DNA sequencing was performed on the Illumina platform (Illumina HiSeq). Reads were mapped to the hg19 reference genome, and variants were called and annotated using Genome Analysis Toolkit (GATK), ANNOVAR, and custom pipelines. Candidate variants were confirmed in other family members and 400 control women. Sanger sequencing of candidate genes in 200 independent sporadic patients with POI were performed to detect other variations in those genes.