title: Observed and expected frequencies of structural hemoglobin variants in newborn screening surveys in Africa and the Middle East: deviations from Hardy-Weinberg equilibrium.
abstract: OBJECTIVE
  Our objective was to compare observed and expected genotype proportions from newborn screening surveys of structural hemoglobin variants.
  
  
  METHODS
  We conducted a systematic review of newborn screening surveys of hemoglobins S and C in Africa and the Middle East. We compared observed frequencies to those expected assuming Hardy-Weinberg equilibrium (HWE). Significant deviations were identified by an exact test. The fixation index FIS was calculated to assess excess homozygosity. We compared newborn estimates corrected and uncorrected for HWE deviations using demographic data.
  
  
  RESULTS
  Sixty samples reported genotype counts for hemoglobin variants in Africa and the Middle East. Observed and expected counts matched in 27%. The observed number of sickle cell anemia (SCA) individuals was higher than expected in 42 samples, reaching significance (P < 0.05) in 24. High FIS values were common across the study regions. The estimated total number of newborns with SCA, corrected based on FIS, was 33,261 annual births instead of 24,958 for the 38 samples across sub-Saharan Africa and 1,109 annual births instead of 578 for 12 samples from the Middle East.
  
  
  CONCLUSIONS
  Differences between observed and expected genotype frequencies are common in surveys of hemoglobin variants in the study regions. Further research is required to identify and quantify factors responsible for such deviations. Estimates based on HWE might substantially underestimate the annual number of SCA-affected newborns (up to one-third in sub-Saharan Africa and one-half in the Middle East).
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK.
authors.forename: Frédéric B
authors.identifier: http://orcid.org/0000-0001-8131-7728
authors.initials: FB
authors.lastname: Piel
authors.affiliation: Department of Family Medicine, Morehouse School of Medicine, Atlanta, Georgia, USA.
authors.forename: Thomas V
authors.initials: TV
authors.lastname: Adamkiewicz
authors.affiliation: African Population and Health Research Center, Nairobi, Kenya.
authors.forename: Djesika
authors.initials: D
authors.lastname: Amendah
authors.affiliation: Kenya Medical Research Institute-Wellcome Trust Programme, Centre for Geographic Medicine Research-Coast, Kilifi District Hospital, Kilifi, Kenya.|Department of Medicine, Imperial College, St Mary's Hospital, London, UK.
authors.forename: Thomas N
authors.identifier: http://orcid.org/0000-0003-4456-2382
authors.initials: TN
authors.lastname: Williams
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK.
authors.forename: Sunetra
authors.initials: S
authors.lastname: Gupta
authors.affiliation: National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Scott D
authors.identifier: http://orcid.org/0000-0003-1078-6855
authors.initials: SD
authors.lastname: Grosse
mesh_terms: D000349:Africa / Q000453:epidemiology; D000755:Anemia, Sickle Cell / Q000453:epidemiology / Q000235:genetics*; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006306:Health Surveys; D006444:Hemoglobin C / Q000235:genetics*; D006451:Hemoglobin, Sickle / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008877:Middle East / Q000453:epidemiology; D015997:Neonatal Screening / Q000379:methods*
chemical_list: D006451:Hemoglobin, Sickle; D006444:Hemoglobin C