Table 1.
Replication or generalization of 15 of the fine-mapped 36 BMI loci on the MetaboChip to 35,606 African Americans
| Index-Lead SNPS r2 range****
|
|||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Gene | Chr | Marker Type | rsID | Bp37 | A1 | A2 | Freq | Effect (%) | StdErr (%) | P*** | I2 | HetP | N | In ARIC | In WHI EA |
| SEC16B | 1 | Index, Lead | rs543874 | 177,889,480 | g | a | 0.249 | 1.37 | 0.17 | 6.0E-15 | 44.5 | 4.2E-02 | 35,604 | 0.32–1 (same) | 0.96–1 (same) |
| TMEM18 | 2 | Index | rs13021737 | 632,348 | g | a | 0.883 | 1.36 | 0.23 | 8.9E-09 | 26.8 | 1.7E-01 | 35,541 | 0.42–1.00 | 1.00 |
| Lead | rs10865549 | 631,759 | a | g | 0.883 | 1.52 | 0.24 | 6.4E-10 | 0 | 5.0E-01 | 33,352 | ||||
| BRE*,** | 2 | Index, Lead | rs116612809 | 28,301,171 | g | a | 0.097 | 1.39 | 0.25 | 6.4E-08 | 0 | 6.3E-01 | 35,583 | 1 (same) | 1 (same) |
| COBLL1* | 2 | Index, Lead | rs10184004 | 165,508,389 | t | c | 0.719 | 0.72 | 0.17 | 2.1E-05 | 32.2 | 1.2E-01 | 35,598 | 1 (same) | 1 (same) |
| ETV5 | 3 | Index | rs1516725 | 185,824,004 | c | t | 0.817 | 0.64 | 0.20 | 1.2E-03 | 6.9 | 3.8E-01 | 35,485 | 0.18 | 0.57 |
| Lead | rs7647305 | 185,834,290 | c | t | 0.594 | 0.68 | 0.15 | 1.1E-05 | 0 | 5.3E-01 | 35,602 | ||||
| GNPDA2 | 4 | Index | rs10938397 | 45,182,527 | g | a | 0.250 | 0.77 | 0.17 | 8.4E-06 | 51.9 | 1.5E-02 | 35,517 | 0.22–0.98 | – |
| Lead | rs181153926 | 45,165,656 | t | c | 0.249 | 0.87 | 0.18 | 1.6E-06 | 44.5 | 4.8E-02 | 32,146 | ||||
| POC5 | 5 | Index | rs2112347 | 75,015,242 | t | g | 0.495 | 0.09 | 0.15 | 5.5E-01 | 0 | 8.9E-01 | 35,604 | 0.09 | 0.36 |
| Lead | rs984976 | 74,910,870 | a | g | 0.150 | 0.88 | 0.22 | 5.4E-05 | 0 | 5.2E-01 | 35,595 | ||||
| TFAP2B | 6 | Index | rs2207139 | 50,845,490 | g | a | 0.096 | 0.79 | 0.26 | 2.0E-03 | 44.7 | 4.1E-02 | 35,605 | 0.19 | 0.47 |
| Lead | rs2744475 | 50,784,880 | g | c | 0.331 | 0.84 | 0.16 | 2.0E-07 | 7.5 | 3.7E-01 | 35,513 | ||||
| SLC22A3* | 6 | Index | rs3127574 | 160,791,370 | c | g | 0.587 | 0.03 | 0.15 | 8.3E-01 | 4 | 4.1E-01 | 35,597 | <0.01 | <0.01 |
| Lead | rs116859471 | 160,736,564 | t | a | 0.002 | 7.37 | 1.95 | 2.4E-04 | 53.3 | 1.8E-02 | 33,916 | ||||
| TCF7L2* | 10 | Index, Lead | rs7903146 | 114,758,349 | c | t | 0.706 | 0.66 | 0.17 | 6.1E-05 | 26.7 | 1.8E-01 | 35,604 | 1 (same) | 1 (same) |
| BDNF-AS1/BDNF | 11 | Index | rs11030104 | 27,684,517 | a | g | 0.951 | 1.28 | 0.36 | 3.8E-04 | 14.6 | 3.0E-01 | 35,606 | 0.02–0.05 | <0.01 |
| Lead | rs7929344 | 27,743,495 | a | g | 0.245 | 0.78 | 0.18 | 1.1E-05 | 28.5 | 1.6E-01 | 35,586 | ||||
| MAP2K5 | 15 | Index | rs16951275 | 68,077,168 | t | c | 0.610 | 0.57 | 0.15 | 2.7E-04 | 0 | 5.7E-01 | 35,605 | 0.52–0.93 | 0.53–0.99 |
| Lead | rs3784718 | 68,098,004 | c | t | 0.630 | 0.61 | 0.16 | 1.2E-04 | 0 | 5.9E-01 | 34,268 | ||||
| ATP2A1 | 16 | Index | rs2650492 | 28,333,411 | a | g | 0.064 | 0.70 | 0.33 | 3.5E-02 | 0 | 5.3E-01 | 35,590 | 0.82 | 1.00 |
| Lead | rs8061590 | 28,895,130 | g | a | 0.312 | 0.69 | 0.16 | 2.5E-05 | 29.8 | 1.5E-01 | 35,592 | ||||
| FTO | 16 | Index | rs17817964 | 53,828,066 | t | c | 0.118 | 1.05 | 0.24 | 1.2E-05 | 33 | 1.2E-01 | 35,606 | 0.91–0.98 | 0.94–1.00 |
| Lead | rs62048402 | 53,803,223 | a | g | 0.114 | 1.19 | 0.24 | 1.1E-06 | 23 | 2.1E-01 | 35,603 | ||||
| MC4R | 18 | Index, Lead | rs6567160 | 57,829,135 | c | t | 0.189 | 1.08 | 0.19 | 2.8E-08 | 58.9 | 3.7E-03 | 35,599 | <0.01–1 (same) | <0.01–1 (same) |
Abbreviations: ARIC=Atherosclerosis Risk in Communities Study, Bp37=base pair Build 37, Chr=chromosome, EA=European American women, Freq=Frequency of A1, 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 African descent signal (Gong et al. 2013).
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. ARIC and WHI samples were used to represent the linkage disequilibrium for the PAGE African and European descent samples.