Supplemental Data for "Modeled Fetal Risk of Genetic Diseases Identified by Expanded Carrier Screening"

Data file accompanying: Haque IS, Lazarin GA, Kang HP, Evans EA, Goldberg JD, Wapner RJ. Modeled Fetal Risk of Genetic Diseases Identified by Expanded Carrier Screening. JAMA. 2016;316(7):734-742. doi:10.1001/jama.2016.11139

(SRC = self-reported racial/ethnic category; TG = targeted genotyping; NGS = next-generation sequencing)

Data file includes:

• Couple Data: Number of self-identified reproductive couples, separated by tandem or sequential screening status and by (mother SRC, father SRC)
• Disease Severity: List of all diseases tested with severity rating as used in the manuscript.
• Allele Data: Listing of all alleles considered pathogenic in manuscript's data analysis, with number of observations and number of tested chromosomes in each SRC.
• Chromosome Frequencies: for each disease in each SRC:
  • Effective total chromosome count (effective sample size after integrating TG and NGS-only alleles).
  • Beta posterior a,b: parameters a, b for the best-fit beta distribution approximating the probability that a random chromosome in this SRC carries a pathogenic allele (integrating both TG and NGS alleles).
  • # Chromosomes total/positive for TG alleles
  • # Chromosomes total/positive for NGS alleles
  • # Chromosomes total/positive for individuals tested by TG
  • # Chromosomes total/positive for individuals tested by NGS
• Disease Risks: for each disease in each pairing of SRCs
  • Father/Mother computed carrier frequency: probability that a random individual from father/mother's SRC is a carrier for the given disease
  • Computed risk of affected conceptus (mean, 2.5, 97.5 percentiles): mean and CI of the posterior distribution over the probability that a random conceptus arising from the racial/ethnic pairing indicated would be homozygous or compound heterozygous for pathogenic alleles for the indicated disease.
  • Computed carrier couple frequency: probability that a random couple from the given SRCs would be a carrier couple for the indicated disease (ie, that both members of the couple would be carriers for the indicated disease)
  • Total couples: number of tandemly-tested couples of the indicated SRC pairing who both had the "routine carrier testing" indication for testing and were both tested for the given disease
  • Number of carrier couple: from the set of "Total couples", the number of couples in which both members were carriers for the indicated disease
  • Number of carrier couples expected: based on computed carrier couple frequency and number of tested couples, the expected number of carrier couples under the model described in sections 4.3.2 and 4.4 of the supplement.
  • P-value: probability that the number of observed carrier couples or a more extreme count would have occurred by chance, given the posterior distribution over carrier couple counts (see section 4.4 of the supplement). One-tailed p-value.