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Table 1 Genome-wide association studies showing the association of SNPs with vitamin B12 concentrations. Genome-wide association studies testing the association between SNPs and vitamin B12 concentrations. The chromosome location, gene name, reference SNP cluster ID, sample size and ethnicity, mean age, observed frequency of the minor allele in the population, effect size and P value are shown in the table. The order of SNPs reflects the order of the chromosome location

From: An update on vitamin B12-related gene polymorphisms and B12 status

Chromosome location Gene name (gene symbol) Reference SNP cluster ID Sample size and ethnicity Age (years) Minor allele + minor allele frequency Effect size P value References
1p34.1 Methylmalonic aciduria and homocystinuria type C protein (MMACHC) rs12272669 Icelandic sample: n = 37,283 63 ± 24 A = 0.002 Effect: A allele
Other: G allele
β = 0.51 pmol/l
3.00 × 10−9 Grarup et al. [12]
1q42.2 Intergenic rs583228 Initial sample: n = 1999
Chinese Han men
38 ± 11 T = 0.220 Effect: T allele
Other: C allele
β = not available
7.68 × 10−6 Lin et al. [19]
Replication sample: n = 1496
Chinese men
37 ± 11 Effect: T allele
Other: C allele
β = not available
> 0.05
Combined total: n = 3495   Effect: T allele
Other: C allele
β = 25.50 pg/ml
SE = 7.19
3.92 × 10−4
2q34 Carbamoyl-phosphate synthase 1 (CPS1) rs1047891 Icelandic sample: n = 37,283 63 ± 24 A = 0.372 Effect: C allele
Other: A allele
β = 0.04 pmol/l
7.60 × 10−6 Grarup et al. [12]
Danish Inter99 population: n = 5481 46 ± 8 Effect: C allele
Other: A allele
β = 0.10 pmol/l
5.50 × 10−4
Danish Health 2006: n = 2812 49 ± 13 Effect: C allele
Other: A allele
β = 0.03 pmol/l
> 0.05
Combined total: n = 45,574   Effect: C allele
Other: A allele
β = not available
3.00 × 10−8
4q31.21 Methylmalonic aciduria (cobalamin deficiency) cblA type (MMAA) rs2270655 Parents of PMNS cohort*: n = 1001
Indian
36 ± 5 C = 0.157# Effect allele: C
β = − 0.07 pmol/l
> 0.05 Nongmaithem et al. [22]
adults: n = 724
Indian
38 ± 11 Effect allele: C
β = 0.00 pmol/l
> 0.05
PMNS children*: n = 690
Indian
11 ± 1 Effect allele: C
β = − 0.09 pmol/l
> 0.05
PS children: n = 534
Indian
5 ± 0 Effect allele: C
β = − 0.20 pmol/l
2.00 × 10−2
4q31.21 Methylmalonic aciduria (cobalamin deficiency) cblA type (MMAA) rs2270655 Icelandic sample: n = 37,283 63 ± 24 C = 0.059 Effect: G allele
Other: C allele
β = 0.07 pmol/l
3.50 × 10−5 Grarup et al. [12]
Danish Inter99 population: n = 5481 46 ± 8 Effect: G allele
Other: C allele
β = 0.30 pmol/l
2.80 × 10−7
Danish Health 2006: n = 2812 49 ± 13 Effect: G allele
Other: C allele
β = 0.25 pmol/l
5.80 × 10−8
Combined total: n = 45,576   Effect: G allele
Other: C allele
β = not available
2.20 × 10−13
4q31.21 Methylmalonic aciduria (cobalamin deficiency) cblA type (MMAA) rs114699496 Icelandic sample: n = 25,960 63 ± 24 T = 0.046** Effect: T
Other: C
β = − 0.07 pmol/l
7.60 × 10−6 Grarup et al. [12]
5q32 Intergenic rs10515552 Initial sample: n = 1999
Chinese Han men
38 ± 11 C = 0.162 Effect: C allele
Other: T allele
β = not available
8.52 × 10−7 Lin et al. [19]
Replication sample: n = 1496
Chinese men
37 ± 11 Effect: C allele
Other: T allele
β = not available
5.15 × 10−3
Combined total: n = 3495   Effect: C allele
Other: T allele
β = 43.93 pg/ml
SE = 7.98
3.94 × 10−8
6p12.3 Methylmalonyl-CoA Mutase (MUT) chr6:49,508,102 Icelandic sample: n = 25,960 63 ± 24 Not available Effect: C allele
Other: G allele
β = 0.07 pmol/l
1.60 × 10−18 Grarup et al. [12]
6p12.3 Methylmalonyl-CoA Mutase (MUT) rs1141321 (rs9473558) Icelandic sample: n = 37,283 63 ± 24 T = 0.373 Effect: C allele
Other: T allele
β = 0.06 pmol/l
1.40 × 10−16 Grarup et al. [12]
Danish Inter99 population: n = 5481 46 ± 8 Effect: C allele
Other: T allele
β = 0.12 pmol/l
1.40 × 10−5
Danish Health 2006: n = 2812 49 ± 13 Effect: C allele
Other: T allele
β = 0.11 pmol/l
1.40 × 10−7
Combined total:
n = 45,574
  Effect: C allele
Other: T allele
β = not available
3.60 × 10−26
6p12.3 Methylmalonyl-CoA mutase (MUT) rs1141321 (rs9473558) Initial sample: n = 1999
Chinese Han men
38 ± 11 T = 0.237 Effect: T allele
Other: C allele
β = − 30.34 pg/ml
SE = 8.91
5.51 × 10−4 Lin et al. [19]
6p12.3 Methylmalonyl-CoA mutase (MUT) rs1141321 (rs9473558) NHS-CGEMS: n = 1658
Caucasian women
59 ± 6 T = 0.350 Effect: T allele
Other: C allele
β = − 0.03 pg/ml
SE = 0.01
4.27 × 10−2 Hazra et al. [20]
SHARe§: n = 1647
Caucasian women
59 ± 10 Effect: T allele
Other: C allele
β = − 0.03 pg/ml
SE = 0.01
1.87 × 10−2
SHARe§: n = 1458
Caucasian men
59 ± 10 Effect: T allele
Other: C allele
β = − 0.07 pg/ml
SE = 0.01
3.96 × 10−7
Combined total: n = 4763   Effect: T allele
Other: C allele
β = − 0.04 pg/ml
SE = 0.01
4.05 × 10−8
6p12.3 Methylmalonyl-CoA mutase (MUT) rs9473555 Icelandic sample: n = 25,960 63 ± 24 C = 0.402 Effect: C allele
Other: G allele
β = − 0.06 pmol/l
5.40 × 10−17 Grarup et al. [12]
6p12.3 Methylmalonyl-CoA mutase (MUT) rs9473555 Initial sample: n = 1999
Chinese Han men
38 ± 11 C = 0.238 Effect: C allele
Other: G allele
β = − 31.00 pg/ml
SE = 8.860
4.06 × 10−4 Lin et al. [19]
6p12.3 Methylmalonyl-CoA mutase (MUT) rs9473555 NHS-CGEMS: n = 1658
Caucasian women
59 ± 6 C = 0.350 Effect: C allele
Other: G allele
β = − 0.03 pg/ml
SE = 0.01
4.27 × 10−2 Hazra et al. [20]
SHARe§: n = 1647
Caucasian women
59 ± 10 Effect: C allele
Other: G allele
β = − 0.03 pg/ml
SE = 0.01
2.26 × 10−2
SHARe§: n = 1458
Caucasian men
59 ± 10 Effect: C allele
Other: G allele
β = − 0.07 pg/ml
SE = 0.01
3.71 × 10−7
Combined total: n = 4763   Effect: C allele
Other: G allele
β = − 0.04 pg/ml
SE = 0.01
4.91 × 10−8
6q15 Nearest gene: sperm acrosome associated 1 (SPACA1) Chr6_88,792,234 Icelandic sample: n = 37,283 63 ± 24 G = 0.006 Effect: G allele
Other: A allele
β = 0.26 pmol/l
2.80 × 10−7 Grarup et al. [12]
7q21.3 Paraoxonase 1 (PON1) rs3917577 n = 3114
Canadian (85% Causasian, 15% non-Caucasian)
20–79 (range) G = 0.020 Effect:A allele
Other: G allele
Vitamin B-12 below adequate (< 220 pmol/l): OR 0.67 (95% CI 0.54, 0.81) pmol/l
7.20 × 10−5 Zinck et al. [18]
8q21.13 Nearest gene: zinc finger and BTB domain containing 10 (ZBTB10) rs62515066 Icelandic sample: n = 37,283 63 ± 24 G = 0.025 Effect: G allele
Other: A allele
β = 0.12 pmol/l
5.40 × 10−7 Grarup et al. [12]
9p21.1 None (Intergenic) rs12377462 Initial sample: n = 1999
Chinese Han men
38 ± 11 T = 0.366 Effect: T allele
Other: C allele
β = not available
3.34 × 10−7 Lin et al. [19]
Replication sample: n = 1496
Chinese men
37 ± 11 Effect: T allele
Other: C allele
β = not available
> 0.05
Combined total: n = 3495   Effect: T allele
Other: C allele
β = 28.53 pg/ml
SE = 5.99
2.02 × 10−6
10p12.31 Cubulin (CUBN) rs1801222 n = 3114
Canadian (85% Causasian, 15% non-Caucasian)
20–79 (range) A = 0.100 Effect: G allele
Other: A allele
Vitamin B12 deficiency (<  148 pmol/l): OR 1.61 (95% CI
1.24, 2.09) pmol/l
3.00 × 10−4 Zinck et al. [18]
10p12.31 Cubulin (CUBN) rs1801222 n = 3114
Canadian (85% Causasian, 15% non-Caucasian)
20–79 (range) A = 0.100 Effect: G allele
Other: A allele
Vitamin B-12 below adequate (< 220 pmol/l): OR 1.39 (95% CI 1.23, 1.58) pmol/l
2.00 × 10−7 Zinck et al. [18]
10p12.31 Cubulin (CUBN) rs1801222 Icelandic sample: n = 37,283 63 ± 24 A = 0.407 Effect: G allele
Other: A allele
β = 0.10 pmol/l
1.10 × 10−52 Grarup et al. [12]
Danish Inter99 population: n = 5481 46 ± 8 Effect: G allele
Other: A allele
β = 0.14 pmol/l
7.60 × 10−8
Danish Health 2006: n = 2812 49 ± 13 Effect: G allele
Other: A allele
β = 0.17 pmol/l
2.90 × 10−18
Combined total: n = 45,576   Effect: G allele
Other: A allele
β = not available
3.30 × 10−75
10p12.31 Cubulin (CUBN) rs1801222 NHS-CGEMS: n = 1658
Caucasian women
59 ± 6 A = 0.280 Effect: A allele
Other: G allele
β = − 0.05 pg/ml
SE = 0.01
9.04 × 10−5 Hazra et al. [20]
SHARe§: n = 1647
Caucasian women
59 ± 10 Effect: A allele
Other: G allele
β = − 0.04 pg/ml
SE = 0.02
6.32 × 10−3
SHARe§: n = 1458
Caucasian men
59 ± 10 Effect: A allele
Other: G allele
β = − 0.05 pg/ml
SE = 0.02
3.56 × 10−4
Combined total: n = 4763   Effect: A allele
Other: G allele
β = − 0.05 pg/ml
SE = 0.01
2.87 × 10−9
10p12.31 Cubulin (CUBN) rs4748353 n = 3114
Canadian (85% Causasian, 15% non-Caucasian)
20–79 (range) C = 0.000 Effect: C allele
Other: T allele
Vitamin B12 deficiency (< 148 pmol/l): OR 2.14 (95% CI 1.36, 3.37) pmol/l
8.00 × 10−4 Zinck et al. [18]
10p12.31 Cubulin (CUBN) rs11254363 n = 3114
Canadian (85% Causasian, 15% non-Caucasian)
20 – 79 (range) G = 0.010 Effect: A allele
Other: G allele
Vitamin B-12 below adequate (< 220 pmol/l): OR 0.81 (95% CI 0.70, 0.93) pmol/l
3.00 × 10−3 Zinck et al. [18]
10p12.31 Cubulin (CUBN) rs11254363 GWAS Meta-analysis: InCHIANTI study: n = 1175
Italian
SardiNIA study: n = 1115
Italian
BLSA study: n = 640
Residents from the USA
InCHIANTI: 68 ± 16
SardiNIA: 45 ± 18
BLSAg: 68 ± 16
G = 0.300 Effect: A allele
Other: G allele
β = − 39.16 pg/ml
SE = 9.18
7.24 × 10−8 Tanaka et al. [21]
Replication study: Progetto Nutrizione study: n = 687
Italian
47 ± 13 Effect: A allele
Other: G allele
β = 3.62 pg/ml
SE = 10.94
> 0.05
Combined meta-analysis (GWAS Meta-analysis + Replication study): n = 3613   Effect: A allele
Other: G allele
β = − 21.49 pg/ml
SE = 7.03
1.11 × 10−6
10p12.31 Cubulin (CUBN) rs12243895 Initial sample: n = 1999
Chinese Han men
38 ± 11 A = 0.243 Effect: A allele
Other: G allele
β = 23.49 pg/ml
SE = 9.06
7.11 × 10−3 Lin et al. [19]
10p12.31 Cubulin (CUBN) rs12780845 Parents of PMNS cohort*: n = 1001
Indian
36 ± 5 G = 0.415# Effect allele: G
β = 0.09 pmol/l
> 0.05 Nongmaithem et al. [22]
Adults: n = 724
Indian
38 ± 11 Effect allele: G
β = 0.09 pmol/l
> 0.05
PMNS children*: n = 690
Indian
11 ± 1 Effect allele: G
β = 0.08 pmol/l
> 0.05
PS children: n = 534
Indian
5 ± 0 Effect allele: G
β = 0.03 pmol/l
> 0.05
10p13 DNA methyltransferase gene (DNMT2)/TRNA aspartic acid methyltransferase 1 (TRDMT1) rs2295809 n = 3114
Canadian (85% Causasian, 15% non-Caucasian)
20–79 (range) T = 0.240 Effect: A allele
Other: T allele
Vitamin B-12 below adequate (< 220 pmol/l): OR 0.82 (95% CI 0.73, 0.92) pmol/l
1.00 × 10−3 Zinck et al. [18]
10p13 DNA methyltransferase gene (DNMT2)/TRNA aspartic acid methyltransferase 1 (TRDMT1) rs56077122 Icelandic sample: n = 25,960 63 ± 24 A = 0.335 Effect: A allele
Other: C allele
β = 0.09 pmol/l
4.80 × 10−21 Grarup et al. [12]
11q12.1 Intergenic
Nearest gene: transcobalamin 1 (TCN1)
rs117456053 Icelandic sample: n = 25,960 63 ± 24 A = 0.024 Effect: G allele
Other: A allele
β = 0.16 pmol/l
1.90 × 10−9 Grarup et al. [12]
11q12.1 Membrane Spanning 4-Domains A3 (MS4A3) rs2298585 Icelandic sample: n = 25,960 63 ± 24 T = 0.001 Effect: T allele
Other: C allele
β = 0.21 pmol/l
> 0.05 Grarup et al. [12]
11q12.1 Membrane Spanning 4-Domains A3 (MS4A3) rs2298585 Initial sample: n = 1999
Chinese Han men
38 ± 11 T = 0.120 Effect: T allele
Other: C allele
β = not available
1.71 × 10−10 Lin et al. [19]
Replication sample: n = 1496
Chinese men
37 ± 11 Effect: T allele
Other: C allele
β = not available
1.58 × 10−6
Combined total: n = 3495   Effect: T allele
Other: C allele
β = 71.80 pg/ml
SE = 9.04
2.64 × 10−15
11q12.1 Transcobalamin 1 (TCN1) rs526934 Adults: n = 724
Indian
38 ± 11 G = 0.216# Effect allele: G
β = − 0.07 pmol/l
> 0.05 Nongmaithem et al. [22]
PMNS children*: n = 690
Indian
11 ± 1 Effect allele: G
β = − 0.10 pmol/l
> 0.05
PS children: n = 534
Indian
5 ± 0 Effect allele: G
β = − 0.16 pmol/l
2.00 × 10−2
11q12.1 Transcobalamin 1 (TCN1) rs526934 n = 3114
Canadian (85% Causasian, 15% non-Caucasian)
20–79 (range) G = 0.080 Effect: A allele
Other: G allele
Vitamin B-12 below adequate (< 220 pmol/l):
OR 1.38 (95% CI 1.21, 1.57) pmol/l
1.40 × 10−6 Zinck et al. [18]
11q12.1 Transcobalamin 1 (TCN1) rs526934 Icelandic sample: n = 25,960 63 ± 24 G = 0.296 Effect: G allele
Other: A allele
β = − 0.12 pmol/l
2.30 × 10−48 Grarup et al. [12]
11q12.1 Transcobalamin 1 (TCN1) rs526934 Initial sample: n = 1999
Chinese Han men
8 ± 11 G = 0.189 Effect: G allele
Other: A allele
β = − 30.39 pg/ml
SE = 9.66
1.78 × 10−3 Lin et al. [19]
11q12.1 Transcobalamin 1 (TCN1) rs526934 NHS-CGEMS: n = 1658
Caucasian women
59 ± 6 G = 0.270 Effect: G allele
Other: A allele
β = − 0.05 pg/ml
SE = 0.01
1.27 × 10−3 Hazra et al. [20]
SHARe§:
n = 1647
Caucasian women
59 ± 10 Effect: G allele
Other: A allele
β = − 0.06 pg/ml
SE = 0.02
6.69 × 10−5
SHARe§: n = 1458
Caucasian men
59 ± 10 Effect: G allele
Other: A allele
β = − 0.06 pg/ml
SE = 0.02
1.64 × 10−4
Combined total: n = 4763   Effect: G allele
Other: A allele
β = − 0.05 pg/ml
SE = 0.01
2.25 × 10−10
11q12.1 Transcobalamin 1 (TCN1) rs526934 GWAS Meta-analysis:
InCHIANTI study: n = 1175
Italian
SardiNIA study: n = 1115
Italian
BLSA study: n = 640
Residents from the USA
InCHIANTI: 68 ± 16
SardiNIA: 45 ± 18
BLSAg: 68 ± 16
G = 0.330 Effect: A allele
Other: G allele
β = 36.76 pg/ml
SE = 10.35
8.33 × 10−7 Tanaka et al. [21]
Replication study:
Progetto Nutrizione study: n = 687
Italian
47 ± 14 Effect: A allele
Other: G allele
β = 12.83 pg/ml
SE = 13.24
> 0.05
Combined meta-analysis (GWAS Meta-analysis + Replication study): n = 3613   Effect: A allele
Other: G allele
β = 27.62 pg/ml
SE = 8.15
1.51 × 10−6
11q12.1 Transcobalamin 1 (TCN1) rs34324219 Adults: n = 724
Indian
38 ± 11 A = 0.041†† Effect allele: A
β = − 0.30 pmol/l
2.00 × 10−2 Nongmaithem et al. [22]
PMNS children*: n = 690
Indian
11 ± 1 Effect allele: A
β = − 0.14 pmol/l
> 0.05
PS children: n = 534
Indian
5 ± 0 Effect allele: A
β = − 0.65 pmol/l
9.50 × 10−7
11q12.1 Transcobalamin 1 (TCN1) rs34324219 Icelandic sample: n = 37,283 63 ± 24 A = 0.119 Effect: C allele
Other: A allele
β = 0.21 pmol/l
8.80 × 10−71 Grarup et al. [12]
Danish Inter99 population: n = 5481 46 ± 8 Effect: C allele
Other: A allele
β = 0.40 pmol/l
3.20 × 10−23
Danish Health 2006: n = 2812 49 ± 13 Effect: C allele
Other: A allele
β = 0.30 pmol/l
3.50 × 10−24
Combined total: n = 45,576   Effect: C allele
Other: A allele
β = not available
1.10 × 10−111
11q12.1 Transcobalamin 1 (TCN1) rs34528912 Adults: n = 724
Indian
38 ± 11 T = 0.006†† Effect allele: T
β = − 0.79 pmol/l
1.00 × 10−2 Nongmaithem et al. [22]
PMNS children*: n = 690
Indian
11 ± 1 Effect allele: T
β = 0.38 pmol/l
> 0.05
PS children: n = 534
Indian
5 ± 0 Effect allele: T
β = − 0.47 pmol/l
3.00 × 10−2
11q12.1 Transcobalamin 1 (TCN1) rs34528912 Icelandic sample: n = 25,960 63 ± 24 T = 0.036 Effect: T allele
Other: C allele
β = 0.17 pmol/l
2.10 × 10−15 Grarup et al. [12]
13q32.3 Citrate Lyase Beta Like (CLYBL) rs41281112 Initial sample: n = 1999
Chinese Han men
38 ± 11 T = 0.044 Effect: T allele
Other: C allele
β = not available
1.09 × 10−8 Lin et al. [19]
Replication sample: n = 1496
Chinese men
37 ± 11 Effect: T allele
Other: C allele
β = not available
7.41 × 10−3
Combined total: n = 3495   Effect: T allele
Other: C allele
β = − 83.60 pg/ml
SE = 13.62
9.23 × 10−10
13q32.3 Citrate Lyase Beta Like (CLYBL) rs41281112 Icelandic sample: n = 37,283 63 ± 24 T = 0.052 Effect: C allele
Other: T allele
β = 0.17 pmol/l
9.60 × 10−27 Grarup et al. [12]
Danish Inter99 population: n = 5481 46 ± 8 Effect: C allele
Other: T allele
β = 0.24 pmol/l
1.30 × 10−3
Danish Health 2006: n = 2812 49 ± 13 Effect: C allele
Other: T allele
β = 0.29 pmol/l
2.50 × 10−7
Combined total: n = 45,576   Effect: C allele
Other: T allele
β = not available
8.90 × 10−35
14q24.3 ATP Binding Cassette Subfamily D Member 4 (ABCD4) rs3742801 Icelandic sample: n = 37,283 63 ± 24 T = 0.294 Effect: T allele
Other: C allele
β = 0.05 pmol/l
5.30 × 10−8 Grarup et al. [12]
Danish Inter99 population: n = 5481 46 ± 8 Effect: T allele
Other: C allele
β = 0.09 pmol/l
7.60 × 10−4
Danish Health 2006: n = 2812 49 ± 13 Effect: T allele
Other: C allele
β = 0.08 pmol/l
4.50 × 10−5
Combined total: n = 45,571   Effect: T allele
Other: C allele
β = not available
1.70 × 10−13
14q24.3 ATP binding cassette subfamily D member 4 (ABCD4) rs4619337 Icelandic sample: n = 25,960 63 ± 24 C = 0.292‡‡ Effect: C allele
Other: T allele
β = 0.05 pmol/l
3.40 × 10−8 Grarup et al. [12]
19p13.2 Actin like 9 (ACTL9) rs2340550 Initial sample: n = 1999
Chinese Han men
38 ± 11 A = 0.134 Effect: A allele
Other: G allele
β = not available
9.34 × 10−7 Lin et al. [19]
Replication sample: n = 1496
Chinese men
37 ± 11 Effect: A allele
Other: G allele
β = not available
> 0.05
Combined total: n = 3495   Effect: A allele
Other: G allele
β = 23.39 pg/ml
SE = 8.56
6.32 × 10−3
19p13.2 CD320 molecule (CD320)/transcobalamin II receptor (TcblR) rs2336573 n = 3114
Canadian (85% Causasian, 15% non-Caucasian)
20–79 (range) T = 0.010 Effect: C allele
Other: T allele
Vitamin B-12 below adequate (< 220 pmol/l):
OR 0.62 (95% CI 0.45, 0.86) pmol/l
3.0 × 10−3 Zinck et al. [18]
19p13.2 CD320 molecule (CD320) / Transcobalamin II Receptor (TcblR) rs2336573 Icelandic sample: n = 37,283 63 ± 24 T = 0.031 Effect: T allele
Other: C allele
β = 0.32 pmol/l
1.10 × 10−51 Grarup et al. [12]
Danish Inter99 population: n = 5481 46 ± 8 Effect: T allele
Other: C allele
β = 0.22 pmol/l
5.70 × 10−3
Danish Health 2006: n = 2812 49 ± 13 Effect: T allele
Other: C allele
β = 0.31 pmol/l
1.70 × 10−8
Combined total: n = 45,575   Effect: T allele
Other: C allele
β = not available
8.40 × 10−59
19p13.2 CD320 molecule (CD320) / Transcobalamin II receptor (TcblR) rs8109720 Icelandic sample: n = 25,960 63 ± 24 Not available Effect: G allele
Other: A allele
β = 0.32 pmol/l
5.80 × 10−52 Grarup et al. [12]
19q13.33 Fucosyl transferase 2 gene (FUT2) rs281379 Parents of PMNS cohort*: n = 1001
Indian
36 ± 5 A = 0.222# Effect allele: A
β = 0.20 pmol/l
4.60 × 10−4 Nongmaithem et al. [22]
Adults: n = 724
Indian
38 ± 11 Effect allele: A
β = 0.05 pmol/l
> 0.05
PMNS children*: n = 690
Indian
11 ± 1 Effect allele: A
β = 0.24 pmol/l
4.50 × 10−4
PS children: n = 534
Indian
5 ± 0 Effect allele: A
β = 0.13 pmol/l
> 0.05
19q13.33 Fucosyl transferase 2 gene (FUT2) rs492602 n = 3114
Canadian (85% Causasian, 15% non-Caucasian)
20–79 (range) A = 0.210 Effect: G allele
Other: A allele
Vitamin B12 deficiency (< 148 pmol/l):
OR 0.60 (95% CI 0.54, 0.70) pmol/l
2.00 × 10−4 Zinck et al. [18]
19q13.33 Fucosyl transferase 2 gene (FUT2) rs492602 n = 3114
Canadian (85% Causasian, 15% non-Caucasian)
20–79 (range) A = 0.210 Effect: G allele
Other: A allele
Vitamin B-12 below adequate (< 220 pmol/l):
OR 0.71 (95% CI 0.65, 0.81) pmol/l
9.00 × 10−8 Zinck et al. [18]
19q13.33 Fucosyl transferase 2 gene (FUT2) rs492602 NHS-CGEMS: n = 1658
Caucasian women
59 ± 6 G = 0.440 Effect: G allele
Other: A allele
β = 0.09 pg/ml
SE = 0.01
5.39 × 10−11 Hazra et al. [20]
SHARe§: n = 1647
Caucasian women
59 ± 10 Effect: G allele
Other: A allele
β = 0.04 pg/ml
SE = 0.02
5.89 × 10−3
SHARe§: n = 1458
Caucasian men
59 ± 10 Effect: G allele
Other: A allele
β = 0.05 pg/ml
SE = 0.01
2.36 × 10−4
Combined total: n = 4763   Effect: G allele
Other: A allele
β = 0.06 pg/ml
SE = 0.01
1.30 × 10−14
19q13.33 Fucosyl transferase 2 gene (FUT2) rs492602 NHS-CGEMS: n = 1637
Caucasian women
59 (Mean) G = 0.490 Effect: A allele
Other: G allele
β = − 0.08 pg/ml
SE = 0.01
2.68 × 10−10 Hazra et al. [29]
Replication: n = 1059
Caucasian women
63 (Mean) Effect: A allele
Other: G allele
β = − 0.10 pg/ml
SE = 0.02
5.60 × 10−9
Combined meta-analysis: n = 2696   Effect: A allele
Other: G allele
β = − 0.09 pg/ml
SE = 0.01
5.36 × 10−17
19q13.33 Fucosyl transferase 2 gene (FUT2) rs516316 Icelandic sample: n = 25,960 63 ± 24 C = 0.469‡‡ Effect: C allele
Other: G allele
β = 0.17 pmol/l
3.60 × 10−103 Grarup et al. [12]
19q13.33 Fucosyl transferase 2 gene (FUT2) rs601338 Adults: n = 724
Indian
38 ± 11 A = 0.230# Effect: A
Other: G
β = 0.05 pmol/l
> 0.05 Nongmaithem et al. [22]
PMNS children*: n = 690
Indian
11 ± 1 Effect: A
Other: G
β = 0.25 pmol/l
3.8 × 10−5
PS children: n = 534
Indian
5 ± 0 Effect: A
Other: G
β = 0.18 pmol/l
4.30 × 10−3
19q13.33 Fucosyl transferase 2 gene (FUT2) rs601338 n = 25,960
Icelandic
63 ± 24 G = 0.384 Effect: G allele
Other: A allele
β = − 0.16 pmol/l
2.40 × 10−95 Grarup et al. [12]
19q13.33 Fucosyl transferase 2 gene (FUT2) rs601338 NHS-CGEMS: n = 1658
Caucasian women
59 ± 6 A = 0.450 Effect: A allele
Other: G allele
β = 0.09 pg/ml
SE = 0.01
4.25 × 10−11 Hazra et al. [20]
SHARe§: n = 1647
Caucasian women
59 ± 10 Effect: A allele
Other: G allele
β = 0.05 pg/ml
SE = 0.01
2.63 × 10−3
SHARe§: n = 1458
Caucasian men
59 ± 10 Effect: A allele
Other: G allele
β = 0.05 pg/ml
SE = 0.01
4.02 × 10−4
Combined total: n = 4763   Effect: A allele
Other: G allele
β = 0.06 pg/ml
SE = 0.01
6.92 × 10−15
19q13.33 Fucosyl transferase 2 gene (FUT2) rs601338 NHS-CGEMS: n = 1658
Caucasian women
59 (Mean) G = 0.490 Effect: G allele
Other: A allele
β = − 0.08 pg/ml
SE = 0.01
4.11 × 10−10 Hazra et al. [29]
19q13.33 Fucosyl transferase 2 gene (FUT2) rs602662 Adults: n = 724
Indian
38 ± 11 A = 0.233# Effect allele: A
β = 0.10 pmol/l
> 0.05 Nongmaithem et al. [22]
PMNS children*: n = 690
Indian
11 ± 1 Effect allele: A
β = 0.25 pmol/l
1.90 × 10−5
PS children: n = 534
Indian
5 ± 0 Effect allele: A
β = 0.20 pmol/l
1.40 × 10−3
19q13.33 Fucosyl transferase 2 gene (FUT2) rs602662 n = 3114
Canadian (85% Causasian, 15% non-Caucasian)
20–79 (range) G = 0.230 Effect: A allele
Other: G allele
Vitamin B12 deficiency (< 148 pmol/l):
OR 0.61 (95% CI 0.47, 0.80) pmol/l
3.00 × 10−4 Zinck et al. [18]
19q13.33 Fucosyl transferase 2 gene (FUT2) rs602662 n = 3114
Canadian (85% Causasian, 15% non-Caucasian)
20–79 (range) G = 0.230 Effect: A allele
Other: G allele
Vitamin B-12 below adequate (< 220 pmol/l):
OR 0.74 (95% CI 0.66, 0.84) pmol/l
1.20 × 10−6 Zinck et al. [18]
19q13.33 Fucosyl transferase 2 gene (FUT2) rs602662 Icelandic sample: n = 37,283 63 ± 24 G = 0.404 Effect: A allele
Other: G allele
β = 0.16 pmol/l
4.10 × 10−96 Grarup et al. [12]
Danish Inter99 population: n = 5481 46 ± 8 Effect: A allele
Other: G allele
β = 0.19 pmol/l
3.50 × 10−13
Danish - Health 2006: n = 2812 49 ± 13 Effect: A allele
Other: G allele
β = 0.23 pmol/l
1.90 × 10−34
Combined total n = 45,568   Effect: A allele
Other: G allele
β = not available
2.40 × 10−139
19q13.33 Fucosyl transferase 2 gene (FUT2) rs602662 NHS-CGEMS: n = 1658
Caucasian women
59 ± 6 G = 0.440 Effect: G allele
Other: A allele
β = −  0.08 pg/ml
SE = 0.01
3.09 × 10−10 Hazra et al. [20]
SHARe§: n = 1647
Caucasian women
59 ± 10 Effect: G allele
Other: A allele
β = − 0.05 pg/ml
SE = 0.02
3.80 × 10−4
SHARe§: n = 1458
Caucasian men
59 ± 10 Effect: G allele
Other: A allele
β = −  0.05 pg/ml
SE = 0.01
2.80 × 10−4
Combined total: n = 4763   Effect: G allele
Other: A allele
β = −  0.07 pg/ml
SE = 0.01
1.83 × 10−15
19q13.33 Fucosyl transferase 2 gene (FUT2) rs602662 GWAS Meta-analysis:
InCHIANTI study: n = 1175
Italian
SardiNIA study: n = 1115
Italian
BLSA study: n = 640
Residents from the USA
InCHIANTI:
68 ± 16
SardiNIA:
45 ± 18
BLSAg:
68 ± 16
G = 0.470 Effect: A allele
Other: G allele
β = 44.20 pg/ml
SE = 8.26
2.43 × 10−12 Tanaka et al. [21]
Replication study:
Progetto Nutrizione study: N = 687
Italian
47 ± 13 Effect: A allele
Other: G allele
β = 58.65 pg/ml
SE = 10.43
2.19 × 10−10
Combined meta-analysis (GWAS Meta-analysis + Replication study): n = 3613   Effect: A allele
Other: G allele
β = 49.77 pg/ml
SE = 6.47
2.83 × 10−20
19q13.33 Fucosyl transferase 2 gene (FUT2) rs602662 NHS-CGEMS: n = 1658
Caucasian women
59 (Mean) G = 0.490 Effect: G allele
Other: A allele
β = − 0.08 pg/ml
SE = 0.01
6.54 × 10−10 Hazra et al. [29]
Replication: n = 1056
Caucasian women
63 (Mean)   Effect: G allele
Other: A allele
β = − 0.08 pg/ml
SE = 0.02
1.13 × 10−6
Combined meta-analysis: n = 2714    Effect: G allele
Other: A allele
β = − 0.08 pg/ml
SE = 0.01
3.52 × 10−15
19q13.33 Fucosyl transferase 2 gene (FUT2) rs838133 Adults: n = 724
Indian
38 ± 11 T = 0.205# Effect allele: A
β = 0.05 pmol/l
> 0.05 Nongmaithem et al. [22]
PMNS children*: n = 690
Indian
11 ± 1 Effect allele: A
β = 0.27 pmol/l
2.00 × 10−4
PS children: n = 534
Indian
5 ± 0 Effect allele: A
β = 0.06 pmol/l
> 0.05
19q13.33 Fucosyl transferase 2 gene (FUT2) rs1047781 Initial sample: n = 1999
Chinese Han men
38 ± 11 T = 0.459 Effect: T allele
Other: A allele
β = not available
4.63 × 10−17 Lin et al. [19]
Replication sample: n = 1496
Chinese men
37 ± 11 Effect: T allele
Other: A allele
β = not available
6.79 × 10−22
Combined total: n = 3495   Effect: T allele
Other: A allele
β = 70.21 pg/ml
SE = 5.53
3.62 × 10−36
19p13.3 Fucosyltransferase 6 (FUT6) rs708686 Adults: n = 724
Indian
38 ± 11 T = 0.335# Effect: T allele
β = 0.13 pmol/l
1.0 × 10−2 Nongmaithem et al. [22]
PMNS children*: n = 690
Indian
11 ± 1 Effect: T allele
β = 0.22 pmol/l
2.20 × 10−4
PS children: n = 534
Indian
5 ± 0 Effect: T allele
β = 0.23 pmol/l
2.70 × 10−4
19p13.3 Fucosyltransferase 6 (FUT6) rs708686 n = 25,960
Icelandic
63 ± 24 T = 0.301‡‡ Effect: T allele
Other: C allele
β = 0.05 pmol/l
2.90 × 10−9 Grarup et al. [12]
19p13.3 Fucosyltransferase 6 / Fucosyltransferase 3 (FUT6/FUT3) rs3760775 Parents of PMNS cohort*: n = 1001
Indian
36 ± 5 A = 0.188# Effect allele: A
β = 0.24 pmol/l
6.00 × 10−6 Nongmaithem et al. [22]
Adults: n = 724
Indian
38 ± 11 Effect allele: A
β = 0.24 pmol/l
9.90 × 10−5
PMNS children*: n = 690
Indian
11 ± 1 Effect allele: A
β = 0.31 pmol/l
2.90 × 10−6
PS children: n = 534
Indian
5 ± 0 Effect allele: A
β = 0.24 pmol/l
2.10 × 10−4
19p13.3 Fucosyltransferase 6 (FUT6) rs3760776 Parents of PMNS cohort*: n = 1001
Indian
36 ± 5 T = 0.161# Effect allele: T
β = 0.10 pmol/l
> 0.05 Nongmaithem et al. [22]
Adults: n = 724
Indian
38 ± 11 Effect allele: T
β = 0.23 pmol/l
4.40 × 10−4
PMNS children*: n = 690
Indian
11 ± 1 Effect allele: T
β = 0.30 pmol/l
3.30 × 10−6
PS children: n = 534
Indian
5 ± 0 Effect allele: T
β = 0.18 pmol/l
6.50 × 10−3
19p13.3 Fucosyltransferase 6 (FUT6) rs3760776 n = 25,960 Icelandic 63 ± 24 A = 0.071 Effect: A allele
Other: G allele
β = 0.07 pmol/l
4.40 × 10−6 Grarup et al. [12]
19p13.3 Fucosyltransferase 6
(FUT6)
rs3760776 Initial sample: n = 1999
Chinese Han men
38 ± 11 A = 0.212 Effect: A allele
Other: G allele
β = not available
4.23 × 10−10 Lin et al. [19]
Replication sample: n = 1496
Chinese men
37 ± 11 Effect: A allele
Other: G allele
β = not available
1.98 × 10−4
Combined total: n = 3495   Effect: A allele
Other: G allele
β = 49.78 pg/ml
SE = 6.82
3.68 × 10−13
19p13.3 Fucosyltransferase 6 (FUT6) rs7788053 Icelandic sample: n = 37,283 63 ± 24 A = 0.254 Effect: A allele
Other: G allele
β = 0.05 pmol/l
2.10 × 10−7 Grarup et al. [12]
Danish Inter99 population: n = 5481 46 ± 8 Effect: A allele
Other: G allele
β = 0.05 pmol/l
> 0.05
Danish Health 2006: n = 2812 49 ± 13 Effect: A allele
Other: G allele
β = 0.07 pmol/l
7.20 × 10−4
Combined total: n = 45,575   Effect: A allele
Other: G allele
β = not available
1.70 × 10−10
19p13.3 Fucosyltransferase 6
(FUT6)
rs78060698 Parents of PMNS cohort*: n = 1001
Indian
36 ± 5 A = 0.130†† Effect allele: A
β = 0.21 pmol/l
2.90 × 10−4 Nongmaithem et al. [22]
adults: n = 724
Indian
38 ± 11 Effect allele: A
β = 0.20 pmol/l
3.70 × 10−3
PMNS children*: n = 690
Indian
11 ± 1 Effect allele: A
β = 0.27 pmol/l
1.20 × 10−4
PS children: n = 534
Indian
5 ± 0 Effect allele: A
β = 0.19 pmol/l
8.20 × 10−3
21q22.3 Cystathionine beta synthase (CBS) rs2124459 n = 3114
Canadian (85% Causasian, 15% non-Caucasian)
20–79 (range) C = 0.180 Effect: T allele
Other: C allele
Vitamin B-12 below adequate (< 220 pmol/l):
OR 0.82 (95% CI
0.73, 0.93) pmol/l
2.00 × 10−3 Zinck et al. [18]
22q12.2 Transcobalamin 2 (TCN2) rs757874 n = 3114
Canadian (85% Causasian, 15% non-Caucasian)
20–79 (range) T = 0.080 Effect: G allele
Other: T allele
Vitamin B-12 below adequate (< 220 pmol/l):
OR 1.42 (95% CI 1.11, 1.72) pmol/l
3.30 × 10−4 Zinck et al. [18]
22q12.2 Transcobalamin 2 (TCN2) rs1131603 Adults: n = 724
Indian
38 ± 11 C = 0.023# Effect: C allele
β = 0.43 pmol/l
4.00 × 10−2 Nongmaithem et al. [22]
PMNS children*: n = 690
Indian
11 ± 1 Effect: C allele
β = 0.05 pmol/l
> 0.05
PS children: n = 534
Indian
5 ± 0 Effect: C allele
β = 0.44 pmol/l
5.00 × 10−2
22q12.2 Transcobalamin 2 (TCN2) rs1131603 Icelandic sample: n = 37,283 63 ± 24 C = 0.055 Effect: C allele
Other: T allele
β = 0.19 pmol/l
4.30 × 10−28 Grarup et al. [12]
Danish Inter99 population: n = 5481 46 ± 8 Effect: C allele
Other: T allele
β = 0.33 pmol/l
1.80 × 10−9
Danish Health 2006: n = 2812 49 ± 13 Effect: C allele
Other: T allele
β = 0.33 pmol/l
5.30 × 10−17
Combined total: n = 45,575   Effect: C allele
Other: T allele
β = not available
4.90 × 10−49
22q12.2 Transcobalamin 2 (TCN2) rs5753231 Icelandic sample: n = 25,960 63 ± 24 T = 0.210 Effect: C allele
Other: T allele
β = 0.06 pmol/l
7.50 × 10−10 Grarup et al. [12]
  1. All studies have a cross-sectional study design
  2. SNP single-nucleotide polymorphism
  3. *Pune Maternal Nutrition Study (PMNS)
  4. Parthenon Study (PS)
  5. Nurses’ Health Study (NHS) NCI-Cancer Genetic Markers of Suceptibility (CGEMS) project
  6. §Framingham-SNP-Health Association Resource (SHARe)
  7. Baltimore Longitudinal Study of Aging (BLSA)
  8. #Data refers to the HapMap-GIH population, with data collected from Gujarati Indians from Houston, Texas
  9. **Data refers to European populations collected from: Utah Residents (CEPH) with Northern and Western European Ancestry, Toscani in Italia, Finnish in Finland, British in England and Scotland and Iberian Population in Spain
  10. ††Data refers to South Asian populations collected from: Gujarati Indian from Houston, Texas, Punjabi from Lahore, Pakistan, Bengali from Bangladesh, Sri Lankan Tamil from the UK and Indian Telugu from the UK
  11. Data refers to the HapMap-CEU population, with data collected from Utah Residents (CEPH) with Northern and Western European Ancestry