Modeled Fetal Risk of Genetic Diseases Identified by Expanded Carrier Screening

• Published in: JAMA : the journal of the American Medical Association 2016-08, Vol.316 (7), p.734-742
• Main Authors: Haque, Imran S, Lazarin, Gabriel A, Kang, H. Peter, Evans, Eric A, Goldberg, James D, Wapner, Ronald J
• Format: Article
• Language: English
• Subjects: Asian People - genetics; Black or African American; Black People - genetics; Female; Fetal Diseases - diagnosis; Fetal Diseases - genetics; Genes; Genetic Carrier Screening - methods; Genetic Diseases, Inborn - diagnosis; Genetic Diseases, Inborn - ethnology; Genetic Diseases, Inborn - genetics; Genetic disorders; Genetic testing; Genetic Testing - methods; Genetic Testing - statistics & numerical data; Genotyping Techniques - methods; Heterozygote; Hispanic or Latino - genetics; Homozygote; Humans; Indians, North American - genetics; Jews - genetics; Male; Medical screening; Prenatal care; Quality of care; Retrospective Studies; Statistics, Nonparametric; United States - ethnology; White People - genetics
• ISSN: 0098-7484; 1538-3598; 1538-3598
• DOI: 10.1001/jama.2016.11139

IMPORTANCE: Screening for carrier status of a limited number of single-gene conditions is the current standard of prenatal care. Methods have become available allowing rapid expanded carrier screening for a substantial number of conditions. OBJECTIVES: To quantify the modeled risk of recessive conditions identifiable by an expanded carrier screening panel in individuals of diverse racial and ethnic backgrounds and to compare the results with those from current screening recommendations. DESIGN, SETTING, AND PARTICIPANTS: Retrospective modeling analysis of results between January 1, 2012, and July 15, 2015, from expanded carrier screening in reproductive-aged individuals without known indication for specific genetic testing, primarily from the United States. Tests were offered by clinicians providing reproductive care. EXPOSURES: Individuals were tested for carrier status for up to 94 severe or profound conditions. MAIN OUTCOMES AND MEASURES: Risk was defined as the probability that a hypothetical fetus created from a random pairing of individuals (within or across 15 self-reported racial/ethnic categories; there were 11 categories with >5000 samples) would be homozygous or compound heterozygous for 2 mutations presumed to cause severe or profound disease. Severe conditions were defined as those that if left untreated cause intellectual disability or a substantially shortened lifespan; profound conditions were those causing both. RESULTS: The study included 346 790 individuals. Among major US racial/ethnic categories, the calculated frequency of fetuses potentially affected by a profound or severe condition ranged from 94.5 per 100 000 (95% CI, 82.4-108.3 per 100 000) for Hispanic couples to 392.2 per 100 000 (95% CI, 366.3-420.2 per 100 000) for Ashkenazi Jewish couples. In most racial/ethnic categories, expanded carrier screening modeled more hypothetical fetuses at risk for severe or profound conditions than did screening based on current professional guidelines (Mann-Whitney P