Table 2.
Generalization of 13 of the fine-mapped 36 BMI loci on the MetaboChip to 26,048 Hispanic/Latino Americans
| Index-Lead SNPS r2 range****
|
|||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Gene | Chr | Marker Type | rsID | Bp37 | A1 | A2 | Freq | Effect (%) | StdErr (%) | P*** | ISq | HetP | N | In HCHS/SOL | In WHI EA |
| SEC16B | 1 | Index, Lead | rs543874 | 177,889,480 | g | a | 0.202 | 0.76 | 0.20 | 1.8E-04 | 0 | 4.4E-01 | 26,045 | 0.81–1 (same) | 0.96–1 (same) |
| LYPLAL1** | 1 | Index | rs2820436 | 219,640,680 | a | c | 0.439 | 0.63 | 0.17 | 1.6E-04 | 0 | 4.8E-01 | 26,046 | 0.33 | 0.55 |
| Lead | rs2820446 | 219,748,818 | g | c | 0.414 | 0.89 | 0.17 | 1.3E-07 | 50.8 | 5.8E-02 | 25,991 | ||||
| TMEM18 | 2 | Index | rs13021737 | 632,348 | g | a | 0.867 | 1.14 | 0.24 | 3.6E-06 | 29.5 | 2.0E-01 | 26,016 | 0.82–0.88 | 1.00 |
| Lead | rs6744653 | 628,524 | g | a | 0.849 | 1.25 | 0.23 | 8.5E-08 | 43.9 | 9.8E-02 | 26,047 | ||||
| COBLL1* | 2 | Index | rs10184004 | 165,508,389 | t | c | 0.326 | 0.39 | 0.18 | 3.2E-02 | 44 | 9.7E-02 | 26,045 | 0.67 | 0.45 |
| Lead | rs12692738 | 165,558,252 | c | t | 0.252 | 0.77 | 0.20 | 1.1E-04 | 33 | 1.8E-01 | 26,045 | ||||
| IGF2BP2** | 3 | Index | rs11927381 | 185,508,591 | t | c | 0.673 | 0.52 | 0.18 | 3.9E-03 | 23.6 | 2.5E-01 | 25,976 | 0.14 | 0.05 |
| Lead | rs6778126 | 185,405,781 | g | a | 0.515 | 0.63 | 0.17 | 1.5E-04 | 43.9 | 9.8E-02 | 26,043 | ||||
| GNPDA2 | 4 | Index | rs10938397 | 45,182,527 | g | a | 0.372 | 0.70 | 0.17 | 4.7E-05 | 49.1 | 6.7E-02 | 26,020 | 0.45–0.99 | 0.55–0.99 |
| Lead | rs10938398 | 45,186,139 | a | g | 0.371 | 0.72 | 0.17 | 2.9E-05 | 44.5 | 9.4E-02 | 26,048 | ||||
| SLC39A8* | 4 | Index | rs13107325 | 103,188,709 | t | c | 0.046 | 1.03 | 0.39 | 9.5E-03 | 55.2 | 3.7E-02 | 26,048 | 0.29 | 0.26 |
| Lead | rs63519 | 103,202,914 | a | c | 0.142 | 0.85 | 0.24 | 3.4E-04 | 31.6 | 1.9E-01 | 26,048 | ||||
| TCF7L2* | 10 | Index, Lead | rs7903146 | 114,758,349 | c | t | 0.739 | 0.79 | 0.19 | 3.3E-05 | 63.8 | 1.1E-02 | 26,047 | 1 (same) | 1 (same) |
| KCNQ1* | 11 | Index | rs2237897 | 2,858,546 | t | c | 0.200 | 0.82 | 0.22 | 1.4E-04 | 0 | 9.1E-01 | 26,044 | 0.83 | 0.60 |
| Lead | rs60808706 | 2,857,233 | a | g | 0.217 | 0.90 | 0.21 | 1.6E-05 | 0 | 6.2E-01 | 26,045 | ||||
| MTCH2 | 11 | Index | rs3817334 | 47,650,993 | t | c | 0.397 | 0.51 | 0.17 | 2.5E-03 | 0 | 6.1E-01 | 26,040 | 0.25 | 0.47 |
| Lead | rs11039448 | 47,918,416 | t | g | 0.653 | 0.88 | 0.17 | 4.0E-07 | 0 | 4.7E-01 | 26,048 | ||||
| MAP2K5 | 15 | Index | rs16951275 | 68,077,168 | t | c | 0.531 | 0.37 | 0.17 | 3.4E-02 | 25.4 | 2.4E-01 | 26,046 | <0.01 | <0.01 |
| Lead | rs76616765 | 68,003,745 | g | c | 0.010 | 3.95 | 0.91 | 1.9E-05 | 0 | 6.4E-01 | 24,207 | ||||
| FTO | 16 | Index | rs17817964 | 53,828,066 | t | c | 0.253 | 1.37 | 0.19 | 2.1E-12 | 47.2 | 7.8E-02 | 26,046 | 0.69–0.73 | 0.94–0.98 |
| Lead | rs7187250 | 53,810,546 | a | c | 0.300 | 1.34 | 0.18 | 2.6E-13 | 47.8 | 7.4E-02 | 26,044 | ||||
| MC4R | 18 | Index | rs6567160 | 57,829,135 | c | t | 0.146 | 1.12 | 0.24 | 3.3E-06 | 53 | 4.7E-02 | 26,047 | <0.01–0.79 | <0.01–0.75 |
| Lead | rs72982988 | 57,802,714 | a | g | 0.151 | 1.22 | 0.24 | 2.8E-07 | 16.8 | 3.0E-01 | 26,048 | ||||
Abbreviations: Bp37=base pair Build 37, Chr=chromosome, EA=European American women, Freq=Frequency of A1, HCHS/SOL=Hispanic Community Health Study/Study of Latinos, 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.
Genome-wide significant findings under review (Gong et al., under review at Nature Comm).
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. HCHS/SOL and WHI European American women were used to represent the linkage disequilibrium of the entire PAGE Hispanic/Latino and European descent samples.