Background
Methods
Study cohorts
Kilifi, Kenya (3.5° S, 39.9° E)
Entebbe, Uganda (0.1° N, 32.5° E)
Banfora, Burkina Faso (10.6° N, 4.8° W)
West Kiang, The Gambia (13.3° N, 16.0° W)
Soweto, South Africa (26.2° S, 27.9° E)
Laboratory assays
Definitions
Genotyping and SNP quality control
Statistical analyses
Role of the funding source
Results
Characteristics of study participants
Overall | Kenya | Uganda | Burkina Faso | The Gambia | South Africa | |
---|---|---|---|---|---|---|
No. of participants (%) | 4509 (100%) | 1361 (30.1%) | 1301 (28.9%) | 329 (7.3%) | 629 (13.9%) | 889 (19.7%) |
Median 25(OH)D nmol/L (IQR)a | 77.6 (63.6, 94.2) | 81.0 (66.3, 101.6) | 78.6 (65.1, 94.5) | 78.4 (64.5, 91.3) | 71.2 (59.1, 84.2) | 76.2 (60.6, 91.9) |
Vitamin D status | ||||||
25(OH)D > 150 nmol/l | 79/4509 (1.8%) | 51/1361 (3.7%) | 17/1301 (0.1%) | 4/329 (1.3%) | 1/629 (0.2%) | 6/889 (0.7%) |
25(OH)D > 75 nmol/l | 2485/4509 (55.1%) | 815/1361 (59.9%) | 756/1301 (58.1%) | 186/329 (56.5%) | 265/629 (42.1%) | 463/889 (52.1%) |
25(OH)D 50–75 nmol/l | 1674/4509 (37.1%) | 464/1361 (34.1%) | 479/1301 (36.8%) | 123/329 (37.4%) | 302/629 (48.0%) | 306/889 (34.4%) |
25(OH)D < 50 nmol/l | 350/4509 (7.8%) | 82/1361 (6.0%) | 66/1301 (5.1%) | 20/329 (6.1%) | 62/629 (9.9%) | 120/889 (13.5%) |
25(OH)D < 30 nmol/l | 28/4509 (0.6%) | 4/1361 (0.3%) | 5/1301 (0.4%) | 0/329 (0%) | 2/629 (0.3%) | 17/889 (1.9%) |
Median age (months) | 23.9 (12.3, 35.9) | 19.8 (12.7, 36.8) | 24.1 (23.9, 35.9) | 23.4 (19.7, 26.4) | 46.6 (35.2, 58.7) | 12.0 (11.9, 12.1) |
Age categories (months) | ||||||
< 12 | 816/4509 (18.1%) | 300/1361 (22.0%) | 24/1301 (1.8%) | 19/329 (5.8%) | - | 473/889 (53.2%) |
12–24 | 1597/4509 (35.4%) | 555/1361 (40.8%) | 440/1301 (33.8%) | 172/329 (52.3%) | 15/629 (2.4%) | 415/889 (46.7%) |
24–36 | 1029/450 (22.8%) | 153/1361 (11.2%) | 587/1301 (45.1%) | 138/329 (42.0%) | 150/629 (23.9%) | 1/889 (0.1%) |
36–48 | 478/4509 (10.6%) | 146/1361 (10.7%) | 167/1301 (11.8%) | - | 165/629 (26.2%) | - |
48+ | 589/4509 (13.1%) | 207/1361 (15.2%) | 83/1301 (6.4%) | - | 299/629 (47.5%) | - |
Sex: females | 2216/4509 (49.1%) | 671/1361 (49.3%) | 641/1301 (49.3%) | 161/329 (48.9%) | 297/629 (47.2%) | 446/889 (50.2%) |
Seasoneb | ||||||
Summer/short rains/dry | 867/4503 (19.3%) | 285/1361 (20.9%) | 331/1296 (25.5%) | 72/329 (21.9%) | - | 179/889 (18.1%) |
Autumn/dry | 1475/4503 (32.8%) | 896/1361 (65.8%) | 295/1296 (22.8%) | 123/329 (37.4%) | - | 161/889 (18.1%) |
Winter/long rains | 1361/4503 (30.2%) | 86/1361 (6.3%) | 330/1296 (25.5%) | 129/329 (39.2%) | 536/628 (85.4%) | 280/889 (31.5%) |
Spring/dry | 800/4503 (17.8%) | 94/1361 (6.9%) | 340/1296 (26.2%) | 5/329 (1.5%) | 92/628 (14.7%) | 269/889 (30.3%) |
Nutritional statusc | ||||||
Stunted | 581/2289 (25.4%) | 99/208 (47.6%) | 203/1282 (15.8%) | 103/307 (33.5%) | 176/492 (35.8%) | n/a |
Underweight | 389/2487 (15.6%) | 102/389 (26.2%) | 103/1296 (8.0%) | 58/309 (18.8%) | 126/493 (25.6%) | n/a |
Wasted | 147/2285 (6.4%) | 24/205 (11.7%) | 59/1281 (4.6%) | 20/307 (6.5%) | 44/492 (8.9%) | n/a |
Inflammationd | 1019/4469 (22.8%) | 363/1344 (27.0%) | 306/1285 (23.8%) | 109/322 (33.9%) | 85/629 (13.5%) | 156/889 (17.6%) |
Malariae | 445/3293 (13.5%) | 227/1082 (20.8%) | 89/1280 (7.0%) | 64/303 (21.1%) | 65/628 (10.4%) | n/a |
Vitamin D status
Vitamin D status is associated with age and season, but not with nutritional status
25(OH)D levels (nmol/L)a | Unadjusted regression analyses of 25(OH)D levels | Adjusted regression analyses of 25(OH)D levels | Adjusted logistic regression analyses 25(OH)D < 50 nmol/L | ||||||
---|---|---|---|---|---|---|---|---|---|
Medians (IQR) | Means (95% CI) | Beta (95% CI) | P | R2 | Beta (95% CI) | P | OR (95% CI) | P | |
Age in years | - | - | − 0.05 (− 0.06, − 0.04) | < 0.0001 | 0.045 | − 0.07 (− 0.08, − 0.07) | < 0.0001 | 1.69 (1.52, 1.89) | < 0.0001 |
Sex | |||||||||
Males | 77.7 (64.1, 94.5) | 77.50 (76.52, 78.49) | Ref. | – | Ref. | – | Ref. | – | |
Females | 77.2 (63.0, 94.0) | 76.45 (75.43, 77.48) | − 0.01 (− 0.03, 0.01) | 0.15 | 0.0005 | − 0.02 (− 0.03, 0.001) | 0.066 | 1.32 (1.04, 1.68) | 0.021 |
Country | |||||||||
Kenya | 81.0 (66.3, 101.6) | 81.85 (80.42, 83.30) | Ref. | – | Ref. | – | Ref. | – | |
Uganda | 78.6 (65.1, 94.5) | 78.27 (77.02, 79.54) | − 0.04(− 0.07, − 0.02) | 0.0002 | 0.029 | 0.01 (− 0.02, 0.03) | 0.51 | 0.50 (0.34, 0.74) | 0.001 |
Burkina Faso | 78.4 (64.5, 91.3) | 77.26 (74.98, 79.61) | − 0.06 (− 0.10, − 0.02) | 0.003 | − 0.05 (− 0.08, − 0.01) | 0.012 | 0.81 (0.45, 1.44) | 0.47 | |
The Gambia | 71.2 (59.1, 84.2) | 72.78 (71.15, 74.45) | − 0.15 (− 0.18, − 0.12) | < 0.0001 | 0.09 (0.05, 0.13) | < 0.0001 | 0.29 (0.17, 0.47) | < 0.0001 | |
South Africa | 76.2 (60.6, 91.9) | 70.39 (68.95, 71.86) | − 0.12 (− 0.14, − 0.09) | < 0.0001 | − 0.15 (− 0.18, − 0.12) | < 0.0001 | 2.89 (1.94, 4.29) | < 0.0001 | |
Seasonb | |||||||||
Summer/short rains/dry | 78.8 (64.8, 95.8) | 78.77 (77.19, 80.39) | Ref. | – | Ref. | – | Ref. | – | |
Autumn/dry | 83.6 (67.1, 101.1) | 82.72 (81.43, 84.02) | 0.05 (0.02, 0.07) | 0.0002 | 0.038 | 0.03 (0.01, 0.06) | 0.014 | 0.65 (0.40, 0.96) | 0.032 |
Winter/long rains | 73.3 (60.1, 87.0) | 71.14 (69.96, 72.34) | − 0.10 (− 0.13, − 0.08) | < 0.0001 | − 0.10 (− 0.12, − 0.07) | < 0.0001 | 2.55 (1.75, 3.72) | < 0.0001 | |
Spring/dry | 76.3 (63.1, 91.4) | 75.18 (73.55, 76.84) | − 0.05 (− 0.08, − 0.02) | 0.002 | − 0.05 (− 0.08, − 0.02) | 0.002 | 1.60 (1.07, 2.38 | 0.022 | |
Stuntingc | |||||||||
Not stunted | 77.1 (63.7, 91.0) | 76.13 (75.08, 77.19) | Ref. | – | Ref. | – | Ref. | – | |
Stunted | 73.1 (61.2, 88.4) | 73.58 (71.89, 75.31) | − 0.03 (− 0.06, − 0.01) | 0.015 | 0.003 | − 0.01 (− 0.04, 0.01) | 0.34 | 1.05 (0.69, 1.58) | 0.82 |
Underweightd | |||||||||
Not underweight | 77.2 (63.8, 91.7) | 76.67 (75.72, 77.64) | Ref. | – | Ref. | – | Ref. | – | |
Underweight | 75.6 (61.9, 91.3) | 74.90 (72.68, 77.18) | − 0.02 (− 0.06, 0.01) | 0.15 | 0.0008 | − 0.004 (− 0.04, 0.03) | 0.81 | 0.88 (0.54, 1.40) | 0.58 |
Wastinge> | |||||||||
Not wasted | 76.0 (62.9, 90.6) | 75.32 (74.40, 76.26) | Ref. | – | Ref. | – | Ref. | – | |
Wasted | 79.2 (63.6, 94.5) | 77.81 (74.45, 81.32) | 0.03 (− 0.02, 0.08) | 0.19 | 0.0008 | 0.04 (− 0.01, 0.08) | 0.12 | 0.64 (0.29, 1.38) | 0.25 |
Inflammationf | |||||||||
Without inflammation | 76.4 (62.7, 92.3) | 75.53 (74.74, 76.3) | Ref. | – | Ref. | – | Ref. | – | |
With inflammation | 81.9 (68.0, 99.5) | 82.11 (80.55, 83.69) | 0.08 (0.06, 0.11) | < 0.0001 | 0.012 | 0.07 (0.05, 0.09) | < 0.0001 | 0.59 (0.43, 0.81) | 0.001 |
Malariag | |||||||||
Without malaria | 77.1 (63.1, 92.4) | 76.01 (75.26, 76.77) | Ref. | – | Ref. | – | Ref. | – | |
With malaria | 71.3 (58.9, 85.4) | 71.63 (69.68, 73.63) | − 0.06 (− 0.09, − 0.03) | 0.0001 | 0.004 | − 0.04 (− 0.07, − 0.01) | 0.02 | 1.02 (0.65, 1.61) | 0.93 |
25(OH)D levels are higher with inflammation and lower with malaria
Vitamin D binding protein variants are associated with vitamin D status
Combination of genotypes | DBP Haplotypea | n/total (%) | 25(OH)D levels (nmol/L)c | Unadjusted regression analyses of 25(OH)D levels | Adjusted regression analyses of 25(OH)D levels | Adjusted regression analyses 25(OH)D < 50 nmol/L | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
rs7041 | rs4588 | Medians (IQR) | Means (95% CI) | Beta (95% CI) | P | R2 | Beta (95% CI) | P | OR (95% CI) | P | ||
TT | CC | Gc1f/f | 2689/3851 (69.8%) | 77.7 (63.6, 93.0) | 76.7 (75.8, 77.6) | Ref | – | 0.009 | Ref | – | Ref | – |
TG | CC | Gc1f/s | 514/3851 (13.4%) | 79.2 (65.5, 96.0) | 78.7 (76.6, 80.8) | 0.03 (0.004, 0.05) | 0.092 | 0.03 (− 0.0023, 0.05) | 0.077 | 0.71 (0.47, 1.08) | 0.11 | |
TT | CA | Gc1f/2 | 525/3851 (13.6%) | 72.7 (60.0, 86.8) | 71.6 (69.7, 73.6) | − 0.07 (− 0.10, − 0.04) | < 0.0001 | − 0.08 (− 0.11, − 0.05) | < 0.0001 | 1.79 (1.26, 2.55) | 0.001 | |
GG | CC | Gc1s/s | 38/3851 (1.0%) | 81.8 (61.0, 95.7) | 77.8 (69.7, 86.9) | 0.01 (− 0.08, 0.11) | 0.78 | 0.01 (− 0.09, 0.10) | 0.85 | 0.73 (0.16, 3.29) | 0.69 | |
TG | CA | Gc1s/2 | 66/3851 (1.7%) | 74.6 (59.4, 87.6) | 71.7 (66.1, 77.8) | − 0.07 (− 0.14, − 0.01) | 0.081 | − 0.08 (− 0.15, − 0.01) | 0.026 | 1.18 (0.43, 3.30) | 0.75 | |
TT | AA | Gc2/2 | 19/3851 (0.5%) | 63.9 (52.4, 79.7) | 65.6 (58.0, 74.1) | − 0.16 (− 0.29, − 0.02) | 0.027 | − 0.18 (− 0.37, − 0.04) | 0.009 | 2.34 (0.27, 20.40) | 0.44 | |
Gc variantb | ||||||||||||
T | C | Gc1f | 6417/7702 (83.3%) | 77.3 (63.5, 92.8) | 76.5 (75.9, 77.0) | Ref | – | 0.004 | Ref | – | Ref | – |
G | C | Gc1s | 656/7702 (8.5%) | 78.9 (63.8, 95.5) | 77.9 (76.0, 79.7) | 0.02 (− 0.01, 0.043) | 0.15 | 0.02 (− 0.01, 0.04) | 0.16 | 0.73 (0.52, 1.06) | 0.096 | |
T | A | Gc2 | 629/7702 (8.2%) | 72.4 (59.4, 86.5) | 71.3 (69.5, 73.1) | − 0.07 (− 0.10, − 0.04) | < 0.0001 | − 0.08 (− 0.11, − 0.06) | < 0.0001 | 1.69 (1.23, 2.30) | 0.001 |