Table 3.
Replication or generalization of 11 of the fine-mapped 36 BMI loci on the MetaboChip to 22,465 Asian Americans
| Index-Lead SNPS r2 range****
|
|||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Gene | Chr | Marker Type | rsID | Bp37 | A1 | A2 | Freq | Effect (%) | StdErr (%) | P*** | ISq | HetP | N | In WHI AA | In WHI EA |
| GNPDA2 | 4 | Index | rs10938397 | 45,182,527 | g | a | 0.279 | 0.55 | 0.15 | 2.6E-04 | 24 | 2.3E-01 | 22,386 | 0.69–0.96 | 0.55–0.99 |
| Lead | rs10938398 | 45,186,139 | a | g | 0.281 | 0.57 | 0.15 | 1.6E-04 | 21 | 2.6E-01 | 22,464 | ||||
| Lead (No NA) | rs10938398 | 45,186,139 | a | g | 0.281 | 0.54 | 0.16 | 5.3E-04 | 0 | 4.4E-01 | 19,878 | ||||
| POC5 | 5 | Index | rs2112347 | 75,015,242 | t | g | 0.443 | 0.45 | 0.14 | 9.0E-04 | 10 | 3.5E-01 | 22,464 | 0.62, 0.16 (No NA) | 0.68, 0.64 (No NA) |
| Lead | rs56912706 | 75,037,086 | a | g | 0.517 | 0.57 | 0.13 | 2.2E-05 | 0.4 | 4.3E-01 | 22,464 | ||||
| Lead (No NA) | rs60423072 | 75,006,113 | t | a | 0.825 | 0.74 | 0.19 | 7.1E-05 | 0 | 6.9E-01 | 19,880 | ||||
| CDKAL1*,** | 6 | Index | rs9356744 | 20,685,486 | t | c | 0.595 | 0.86 | 0.14 | 5.3E-10 | 43 | 8.4E-02 | 22,461 | 0.94 | 0.80 |
| Lead | rs9368222 | 20,686,996 | c | a | 0.597 | 0.88 | 0.14 | 2.0E-10 | 39 | 1.1E-01 | 22,393 | ||||
| Lead (No NA) | rs9368222 | 20,686,996 | c | a | 0.603 | 0.90 | 0.14 | 3.7E-10 | 57 | 4.2E-02 | 19,814 | ||||
| TFAP2B | 6 | Index | rs2207139 | 50,845,490 | g | a | 0.210 | 0.29 | 0.17 | 8.5E-02 | 0 | 6.0E-01 | 22,464 | 0.45 | 0.88 |
| Lead | rs2076308 | 50,791,640 | c | g | 0.270 | 0.61 | 0.15 | 6.3E-05 | 0 | 8.0E-01 | 22,461 | ||||
| Lead (No NA) | rs2076308 | 50,791,640 | c | g | 0.276 | 0.63 | 0.16 | 5.6E-05 | 0 | 5.4E-01 | 19,875 | ||||
| TCF7L2* | 10 | Index | rs7903146 | 114,758,349 | c | t | 0.934 | 1.49 | 0.32 | 4.6E-06 | 51 | 4.0E-02 | 22,465 | 0.95 | 0.89 |
| Lead | rs4506565 | 114,756,041 | a | t | 0.931 | 1.50 | 0.32 | 3.7E-06 | 50 | 4.5E-02 | 22,465 | ||||
| Lead (No NA) | rs4506565 | 114,756,041 | a | t | 0.954 | 1.60 | 0.36 | 1.2E-05 | 45 | 1.0E-01 | 19,880 | ||||
| KCNQ1* | 11 | Index | rs2237897 | 2,858,546 | t | c | 0.353 | 0.73 | 0.18 | 3.5E-05 | 62 | 9.9E-03 | 14,181 | 0.83 | 0.83 |
| Lead | rs2299620 | 2,858,295 | t | c | 0.389 | 0.85 | 0.17 | 6.8E-07 | 43 | 9.3E-02 | 14,182 | ||||
| Lead (No NA) | rs2299620 | 2,858,295 | t | c | 0.403 | 0.83 | 0.18 | 3.7E-06 | 59 | 4.7E-02 | 11,604 | ||||
| BDNF-AS1/BDNF | 11 | Index | rs11030104 | 27,684,517 | a | g | 0.566 | 0.10 | 0.14 | 4.5E-01 | 62 | 7.2E-03 | 22,465 | 0.30–0.92 | 0.20–0.98 |
| Lead | rs11030100 | 27,677,586 | g | t | 0.570 | 0.53 | 0.14 | 1.1E-04 | 50 | 4.3E-02 | 22,465 | ||||
| Lead (No NA) | rs11030100 | 27,677,586 | g | t | 0.563 | 0.52 | 0.14 | 3.0E-04 | 68 | 8.1E-03 | 19,879 | ||||
| MTCH2 | 11 | Index | rs3817334 | 47,650,993 | t | c | 0.312 | 0.23 | 0.14 | 1.2E-01 | 0 | 8.7E-01 | 22,447 | 0.03, 0.03 (No NA) | <0.01, 0.01 (No NA) |
| Lead | rs76229852 | 47,258,369 | g | a | 0.958 | 1.48 | 0.34 | 2.0E-05 | 21 | 2.6E-01 | 22,465 | ||||
| Lead (No NA) | rs10838721 | 47,509,017 | a | g | 0.934 | 1.08 | 0.28 | 1.5E-04 | 0 | 6.0E-01 | 19,866 | ||||
| FTO | 16 | Index | rs17817964 | 53,828,066 | t | c | 0.223 | 1.28 | 0.17 | 2.2E-14 | 0 | 4.9E-01 | 22,465 | 0.81–0.98 | 0.95–0.99 |
| Lead | rs3751812 | 53,818,460 | t | g | 0.185 | 1.56 | 0.17 | 5.5E-19 | 0 | 5.4E-01 | 22,463 | ||||
| Lead (No NA) | rs3751812 | 53,818,460 | t | g | 0.180 | 1.52 | 0.18 | 1.4E-16 | 18 | 2.9E-01 | 19,877 | ||||
| MC4R | 18 | Index, Lead | rs6567160 | 57,829,135 | c | t | 0.197 | 0.67 | 0.17 | 9.0E-05 | 0 | 5.8E-01 | 22,461 | <0.01–1 (same) | 0.42 |
| Lead (No NA) | rs6567160 | 57,829,135 | c | t | 0.201 | 0.64 | 0.17 | 2.3E-04 | 0 | 4.4E-01 | 19,875 | ||||
| GIPR* | 19 | Index, Lead | rs11671664 | 46,172,278 | g | a | 0.531 | 0.57 | 0.14 | 4.2E-05 | 0 | 8.4E-01 | 22,460 | 0.02–1 (same) | 0.34–1 (same) |
| Lead (No NA) | rs11671664 | 46,172,278 | g | a | 0.517 | 0.59 | 0.14 | 3.6E-05 | 0 | 6.2E-01 | 19,874 | ||||
Abbreviations: AA=Asian American, Bp37=base pair Build 37, Chr=chromosome, EA=European American women, Freq=Frequency of A1, NA=Native Haiwaiians, SNPs=single nucleotide polymorphisms, WHI=Women's Health Initiative.
Note: Starred genes represent fine-mapped loci, which were associated with BMI after the design of the Metabochip in 2009.
Replication of Asian descent signal (Okada et al 2012, Wen et al. 2012).
For GWAS SNPs a Bonferroni correction for multiple tests reflected the number of independent GWAS signals tested (=0.05/166; Supplemental Table 3). For all other SNPs in the fine-mapped BMI regions, we performed a Bonferroni correction for the number of independent SNPs per region (r2<0.2 in ARIC African-Americans; Supplemental Table 1).
The range of linkage disequilibrium captures any SNP within the fine-mapped loci (Supplemental Table 3) that represents the index BMI signal or secondary signal (described in European descent populations), or race/ethnic population specific marker. WHI Asian and European American women were used to represent the linkage disequilibrium of the entire PAGE Asian and European descent samples.