Observed and expected frequencies of structural hemoglobin variants in newborn screening surveys in Africa and the Middle East: deviations from Hardy-Weinberg equilibrium

Piel FB, Adamkiewicz TV, Amendah D, Williams TN, Gupta S, Grosse SD
Genet Med. 2016;18

Permenent descriptor

PURPOSE: 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. CONCLUSION: 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).