SS indicates sickle cell anemia; NA, not applicable; SSα, sickle cell anemia-α thalassemia; SC, HbSC disease; BEN, Benin; CAR, Central African Republic; SEN, Senegal haplotypes.

Only about 30% of case and control subjects were successfully typed for β-globin gene haplotype; therefore, data are presented as number (% of nonmissing)

The CSSCD used the following definitions for these clinical events. AVN (avascular necrosis of humeral or femoral head) is defined as early radiographic findings of subephiphyseal lucency and widening of the joint space or late radiographic changes of flattening of the epiphysis and sclerosis with fragmentation. ACS (acute chest syndrome) is defined as a new pulmonary infiltrate that is demonstrable on a chest x-ray or by an isotope scan of the lungs, or evidence of pleuritic chest pain, with or without dyspnea, in the absence of a pulmonary infiltrate on the chest x-ray. If pleuritic pain is limited to the chest and chest films are negative, then a perfusion lung scan is required. Acute painful episode is defined as pain in the extremities, back, abdomen, chest, or head, for which no other explanation can be found and which is not classified as one of the other special events. Pain shall have lasted for at least 2 hours. If patient is old enough, he/she must have stated that pain is of nature usually associated with a crisis. Stroke, we only included in our analysis patients with a confirmed history of, or an incident, completed, nonhemorrhagic stroke, documented by imaging studies