Table 3.
X-chromosome SNPs with significant signals of association in different severe malaria phenotypes
| Frequency (%) of derived allele in controls (normal/het/hom [n]) | Frequency (%) of derived allele in cases (normal/het/hom [n]) | Model* |
Unadjusted |
Adjusted† |
|||
|---|---|---|---|---|---|---|---|
| OR (95% CI) | p value | OR (95% CI) | p value | ||||
| CD40LG (rs3092945; T→C) | |||||||
| Severe malaria (male and female) | 21% (2760/646/521) | 26% (1459/388/379) | A | 1·14 (1·06–1·22) | 0·0002 | 1·15 (1·06–1·23) | 0·0002 |
| Cerebral malaria (male and female) | 21% (2760/646/521) | 25% (815/199/209) | A | 1·32 (1·10–1·59) | 0·003 | 1·37 (1·13–1·67) | 0·003 |
| Severe malarial anaemia (male and female) | 21% (2760/646/521) | 26% (442/121/120) | A | 1·17 (1·05–1·31) | 0·0001 | 1·18 (1·05–1·33) | 0·003 |
| Respiratory distress (male and female) | 21% (2760/646/521) | 25% (454/128/98) | A | 1·28 (1·01–1·63) | 0·04 | 1·27 (1·09–1·64) | 0·04 |
| Death (male and female) | 21% (2760/646/521) | 25% (454/128/98) | A | 1·30 (0·88–1·92) | 0·18 | 1·32 (0·88–2·00) | 0·15 |
| CD40LG (rs3092945; T→C) | |||||||
| Severe malaria (female) | 21% (1215/646/81) | 25% (614/388/80) | A | 1·25 (1·10–1·42) | 0·0004 | 1·28 (1·13–1·45) | 0·0002 |
| Cerebral malaria (female) | 21% (1215/646/81) | 26% (355/199/48) | A | 1·89 (1·30–2·76) | 0·001 | 1·23 (1·05–1·43) | 0·007 |
| Severe malarial anaemia (female) | 21% (1215/646/81) | 25% (181/121/26) | A | 1·33 (1·10–1·62) | 0·003 | 1·36 (1·12–1·64) | 0·001 |
| Respiratory distress (female) | 21% (1215/646/81) | 24% (182/128/15) | A | 1·29 (1·01–1·63) | 0·03 | 1·31 (1·03–1·66) | 0·02 |
| Death (female) | 21% (1215/646/81) | 24% (182/128/15) | A | 1·30 (0·88–1·92) | 0·18 | 1·32 (0·90–1·95) | 0·15 |
| CD40LG (rs3092945; T→C) | |||||||
| Severe malaria (male) | 78% (440/0/1545) | 73% (299/0/845) | HM | 0·83 (0·70–0·99) | 0·03 | 0·80 (0·68–0·95) | 0·01 |
| Cerebral malaria (male) | 78% (440/0/1545) | 76% (161/0/460) | HM | 0·84 (0·68–1·04) | 0·11 | 0·81 (0·66–1·00) | 0·05 |
| Severe malarial anaemia (male) | 78% (440/0/1545) | 73% (94/0/261) | HM | 0·81 (0·63–1·05) | 0·12 | 0·79 (0·61–1·02) | 0·07 |
| Respiratory distress (male) | 78% (440/0/1545) | 75% (83/0/272) | HM | 0·95 (0·72–1·23) | 0·71 | 0·93 (0·71–1·21) | 0·61 |
| Death (male) | 78% (440/0/1545) | 75% (83/0/272) | HM | 0·93 (0·62–1·40) | 0·75 | 0·91 (0·61–1·36) | 0·65 |
| G6PD (rs1050828; C→T) | |||||||
| Severe malaria (male and female) | 19% (2863/639/438) | 19% (1643/306/271) | H | 0·82 (0·70–0·97) | 0·01 | 0·80 (0·68–0·96) | 0·01 |
| Cerebral malaria (male and female) | 19% (2863/639/438) | 18% (921/168/131) | H | 0·80 (0·65–0·98) | 0·02 | 0·79 (0·64–0·97) | 0·02 |
| Severe malarial anaemia (male and female) | 19% (2863/639/438) | 23% (479/90/111) | R | 1·60 (1·26–2·03) | 0·0001 | 1·72 (1·33–2·22) | 0·0001 |
| Respiratory distress (male and female) | 19% (2863/639/438) | 18% (510/98/72) | H | 0·90 (0·74–1·09) | 0·28 | 0·91 (0·74–1·11) | 0·28 |
| Death (male and female) | 19% (2863/639/438) | 18% (510/98/72) | H | 0·64 (0·46–0·89) | 0·006 | 0·64 (0·45–0·90) | 0·006 |
| G6PD (rs1050828; C→T) | |||||||
| Severe malaria (female) | 19% (1250/639/62) | 18% (729/306/39) | H | 0·82 (0·70–0·97) | 0·01 | 0·81 (0·69–0·96) | 0·01 |
| Cerebral malaria (female) | 19% (1250/639/62) | 18% (410/168/122) | H | 0·80 (0·65–0·98) | 0·03 | 0·79 (0·65–0·97) | 0·02 |
| Severe malarial anaemia (female) | 19% (1250/639/62) | 17% (224/90/11) | H | 0·79 (0·61–1·03) | 0·07 | 0·78 (0·60–1·02) | 0·06 |
| Respiratory distress (female) | 19% (1250/639/62) | 19% (215/198/12) | H | 0·89 (0·58–1·38) | 0·61 | 0·88 (0·68–1·14) | 0·35 |
| Death (female) | 19% (1250/639/62) | 19% (215/198/12) | H | 0·56 (0·37–0·85) | 0·004 | 0·57 (0·38–0·86) | 0·005 |
| G6PD (rs1050828; C→T) | |||||||
| Severe malaria (male) | 18% (1613/0/376) | 20% (914/0/232) | HM | 1·11 (0·92–1·33) | 0·26 | 1·08 (0·90–1·30) | 0·36 |
| Cerebral malaria (male) | 18% (1613/0/376) | 18% (511/0/109) | HM | 0·92 (0·72–1·17) | 0·48 | 0·91 (0·72–1·15) | 0·45 |
| Severe malarial anaemia (male) | 18% (1613/0/376) | 28% (255/0/100) | HM | 1·72 (1·32–2·23) | 6·98 × 10−5 | 1·68 (1·30–2·17) | 0·0001 |
| Respiratory distress (male) | 18% (1613/0/376) | 17% (295/0/60) | HM | 0·89 (0·66–1·21) | 0·89 | 0·87 (0·64–1·17) | 0·36 |
| Death (male) | 18% (1613/0/376) | 17% (295/0/60) | HM | 0·77 (0·48–1·24) | 0·28 | 0·77 (0·48–1·23) | 0·26 |
Data are from models that were most significant. Individuals with multiple phenotypes are included in each of those phenotype groups for analysis. Analyses were run on males and females separately and combined, using standard meta-analysis techniques. het=heterozygous. hom=homozygous. OR=odds ratio. SNP=single nucleotide polymorphism.
*
Statistical models were additive (A), heterozygous (H), hemizygous male (HM), or recessive (R).
†
Adjusted for ethnic group, gender, and rs334 genotype.