Table 6.
Single variant and joint trans-ethnic fixed-effect estimates for the Bonferroni significant joint signals at the 36 densely-genotyped BMI loci, after accounting for index SNPs (r2<0.9 with each other, included in the trans-ethnic analyses) outside of these regions
| Top SNPS (single variant model)
|
Top SNPS (joint model)
|
GWAS-top joint SNPS |
|||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Gene | rsID | A1 | A2 | Freq | Effect (%) | StdErr (%) | P*** | Isq | HetP**** | Actual n | Aprrox Freq | Effect j (%) | StdErr j (%) | Pj*** | Effective n % | VarExp | r2 range**** in transethnic sample |
| TNNI3K | rs12566985 | g | a | 0.719 | 0.42 | 0.11 | 2.8E-04 | 0 | 5.2E-01 | 75,627 | 0.697 | 0.42 | 0.11 | 1.4E-04 | 85,877 | 0.0007 | 1 (same) |
| SEC16B | rs543874 | g | a | 0.213 | 0.90 | 0.10 | 3.5E-21 | 72.9 | 1.1E-02 | 101,972 | 0.217 | 0.90 | 0.10 | 2.3E-19 | 125,180 | 0.0028 | 0.62–1 (same) |
| LYPLAL1** | rs2820436 | a | c | 0.388 | 0.50 | 0.09 | 3.2E-08 | 0 | 4.7E-01 | 93,721 | 0.387 | 0.50 | 0.09 | 3.5E-08 | 109,170 | 0.0012 | 1 (same) |
| LYPLAL1** | rs4445477 | a | g | 0.621 | 0.38 | 0.10 | 2.5E-04 | 0 | 6.3E-01 | 89,078 | 0.639 | 0.37 | 0.10 | 1.8E-04 | 89,156 | 0.0006 | <0.01 |
| TMEM18 | rs6731872 | g | t | 0.877 | 1.09 | 0.12 | 8.3E-19 | 45.3 | 1.4E-01 | 101,832 | 0.877 | 1.09 | 0.12 | 2.3E-19 | 135,002 | 0.0025 | 0.61–0.92 |
| COBLL1* | rs10184004 | t | c | 0.452 | 0.52 | 0.10 | 1.3E-07 | 0 | 5.5E-01 | 93,726 | 0.444 | 0.53 | 0.11 | 4.0E-07 | 84,752 | 0.0014 | 1 (same) |
| COBLL1* | rs17244444 | g | a | 0.911 | 0.41 | 0.16 | 1.3E-02 | 58.6 | 6.4E-02 | 93,731 | 0.927 | 0.64 | 0.17 | 1.0E-04 | 101,259 | 0.0006 | 0.07 |
| IRS1* | rs2176040 | a | g | 0.275 | 0.50 | 0.10 | 4.0E-07 | 0 | 5.5E-01 | 93,732 | 0.259 | 0.75 | 0.11 | 5.2E-11 | 105,388 | 0.0021 | 1 (same) |
| IRS1* | rs2673147 | c | g | 0.466 | 0.15 | 0.09 | 9.9E-02 | 0 | 8.6E-01 | 93,727 | 0.418 | 0.47 | 0.10 | 4.9E-06 | 104,177 | 0.0011 | 0.23 |
| IGF2BP2** | rs11927381 | t | c | 0.563 | 0.49 | 0.09 | 1.3E-07 | 0 | 8.4E-01 | 93,626 | 0.523 | 0.38 | 0.09 | 4.6E-05 | 105,325 | 0.0007 | 1 (same) |
| ETV5 | rs7647305 | c | t | 0.720 | 0.59 | 0.10 | 3.7E-09 | 0 | 5.2E-01 | 101,974 | 0.744 | 0.48 | 0.10 | 3.1E-06 | 104,120 | 0.0009 | 0.34 |
| GNPDA2 | rs12507026 | t | a | 0.325 | 0.61 | 0.08 | 5.3E-13 | 6.7 | 3.6E-01 | 101,974 | 0.317 | 0.61 | 0.08 | 2.5E-14 | 149,522 | 0.0016 | 0.38–0.98 |
| SLC39A8* | rs28392891 | a | t | 0.891 | 0.52 | 0.15 | 4.8E-04 | 62.3 | 4.7E-02 | 95,585 | 0.913 | 0.51 | 0.15 | 6.9E-04 | 95,771 | 0.0004 | <0.01 |
| SLC39A8* | rs13107325 | t | c | 0.053 | 1.05 | 0.25 | 3.4E-05 | 0 | 8.7E-01 | 79,090 | 0.030 | 1.03 | 0.25 | 4.2E-05 | 67,039 | 0.0006 | 1 (same) |
| POC5 | rs60493905 | c | t | 0.630 | 0.48 | 0.09 | 1.9E-08 | 0 | 7.8E-01 | 101,968 | 0.606 | 0.48 | 0.09 | 9.7E-08 | 111,182 | 0.0011 | 0.17 |
| CDKAL1* | rs67131976 | c | t | 0.729 | 0.60 | 0.10 | 4.0E-10 | 61.6 | 5.0E-02 | 101,973 | 0.798 | 0.60 | 0.10 | 2.0E-09 | 106,176 | 0.0012 | 0.24 |
| TFAP2B | rs2744475 | g | c | 0.352 | 0.56 | 0.08 | 9.9E-12 | 39.1 | 1.8E-01 | 101,763 | 0.349 | 0.54 | 0.08 | 2.1E-11 | 143,714 | 0.0013 | 0.33 |
| TFAP2B | rs2397016 | a | g | 0.806 | 0.76 | 0.17 | 6.8E-06 | 39.6 | 1.9E-01 | 79,510 | 0.909 | 0.68 | 0.17 | 6.8E-05 | 46,410 | 0.0008 | 0.04 |
| LINGO2 | rs17770336 | t | c | 0.223 | 0.52 | 0.10 | 9.6E-08 | 0 | 6.3E-01 | 101,930 | 0.217 | 0.52 | 0.10 | 2.0E-07 | 121,118 | 0.0009 | 0.95 |
| NT5C2* | rs11191447 | t | c | 0.193 | 0.56 | 0.11 | 3.8E-07 | 0 | 8.4E-01 | 101,919 | 0.127 | 0.56 | 0.11 | 3.6E-07 | 111,260 | 0.0007 | 0.86 |
| TCF7L2* | rs7903146 | c | t | 0.739 | 0.75 | 0.10 | 2.2E-13 | 54 | 8.9E-02 | 101,975 | 0.765 | 0.75 | 0.10 | 6.5E-14 | 108,781 | 0.0020 | 1 (same) |
| KCNQ1* | rs2237896 | a | g | 0.272 | 0.73 | 0.13 | 3.0E-08 | 0 | 4.6E-01 | 93,196 | 0.133 | 0.82 | 0.13 | 5.5E-10 | 62,758 | 0.0015 | 0.76 |
| STK33 | rs76633799 | a | g | 0.037 | 1.38 | 0.37 | 2.6E-04 | 0 | 7.1E-01 | 57,988 | 0.017 | 1.45 | 0.37 | 1.1E-04 | 42,922 | 0.0007 | <0.01 |
| TRIM66 | rs76876925 | g | a | 0.512 | 0.36 | 0.10 | 1.4E-04 | 0 | 8.7E-01 | 72,292 | 0.556 | 0.41 | 0.10 | 5.7E-05 | 84,029 | 0.0008 | 0.80 |
| BDNF-AS1 | rs1519480 | c | t | 0.444 | 0.59 | 0.09 | 1.2E-11 | 44.3 | 1.5E-01 | 101,510 | 0.513 | 0.64 | 0.09 | 1.6E-12 | 104,967 | 0.0020 | 0.28–0.40 |
| BDNF | rs190666912 | g | c | 0.496 | 0.35 | 0.09 | 1.9E-04 | 16.9 | 3.0E-01 | 72,303 | 0.502 | 0.43 | 0.09 | 2.6E-06 | 103,685 | 0.0009 | 0.17–0.27 |
| MTCH2 | rs896817 | c | t | 0.713 | 0.46 | 0.09 | 4.3E-07 | 0 | 7.9E-01 | 101,965 | 0.735 | 0.46 | 0.09 | 3.2E-07 | 126,735 | 0.0008 | 0.03 |
| FAIM2 | rs7138803 | a | g | 0.285 | 0.35 | 0.09 | 9.0E-05 | 0 | 4.8E-01 | 101,969 | 0.254 | 0.35 | 0.09 | 1.0E-04 | 127,226 | 0.0005 | 1 (same) |
| MAP2K5 | rs4776970 | a | t | 0.422 | 0.38 | 0.08 | 6.1E-06 | 0 | 9.0E-01 | 101,972 | 0.440 | 0.38 | 0.08 | 2.0E-06 | 134,469 | 0.0007 | 0.56–1 (same) |
| GPRC5B | rs67501351 | g | c | 0.372 | 0.36 | 0.08 | 1.5E-05 | 28.8 | 2.4E-01 | 101,506 | 0.327 | 0.40 | 0.08 | 4.8E-07 | 140,434 | 0.0007 | 0.02 |
| ATP2A1 | rs8061590 | g | a | 0.307 | 0.52 | 0.10 | 2.9E-07 | 0 | 3.7E-01 | 84,081 | 0.318 | 0.56 | 0.10 | 3.2E-08 | 98,598 | 0.0013 | 0.92 |
| FTO | rs3751812 | t | g | 0.242 | 1.34 | 0.10 | 2.4E-42 | 15.6 | 3.1E-01 | 101,974 | 0.213 | 1.31 | 0.13 | 1.8E-24 | 114,260 | 0.0057 | 0.94–0.95 |
| FTO | rs9936385 | c | t | 0.289 | 1.34 | 0.11 | 7.5E-37 | 6.9 | 3.4E-01 | 66,366 | 0.366 | 1.51 | 0.16 | 1.2E-20 | 84,239 | 0.0104 | 0.38–0.39 |
| MC4R | rs6567160 | c | t | 0.193 | 0.89 | 0.10 | 9.4E-19 | 13.8 | 3.2E-01 | 101,966 | 0.184 | 0.89 | 0.10 | 7.7E-19 | 134,789 | 0.0024 | 0.01–1 (same) |
| MC4R | rs77901086 | a | c | 0.985 | 1.84 | 0.43 | 2.6E-05 | 0 | 4.5E-01 | 88,060 | 0.989 | 1.81 | 0.43 | 3.2E-05 | 77,866 | 0.0007 | 0.11 |
| KCTD15 | rs368794 | a | t | 0.537 | 0.32 | 0.08 | 1.4E-04 | 0 | 4.0E-01 | 99,796 | 0.581 | 0.32 | 0.08 | 6.3E-05 | 131,938 | 0.0005 | 0.49 |
| GIPR* | rs1800437 | g | c | 0.817 | 0.64 | 0.11 | 1.6E-09 | 0 | 8.2E-01 | 101,488 | 0.842 | 0.64 | 0.11 | 6.0E-09 | 116,182 | 0.0011 | 0.09–0.88 |
Abbreviations: Bp37=base pair Build 37, Chr=chromosome, FE=Fixed-Effect, MANTRA=Meta-ANalysis of Trans-Ethnic Association studies, SNPs=single nucleotide polymorphisms.
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 reivew 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. ARIC, HCHS/SOL, and WHI samples were used to represent the linkage disequilibrium for the PAGE trans-ethnic and European descent samples.