Table 3. Three densely-genotyped MetaboChip loci with Bonferroni-significant associations with age at menarche across multiple race/ethnic groups or trans-ethnically.
| GWAS Ref | Gene | Chr | Start/Stop BP | P-value* | Index GWAS SNP (Position) | Pop | Top MetaboChip SNP | Position | MA | Freq | Effect (years) | SE | P-value | P-value hetero-geneity | Sam-ple Size |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| [13] | SEC16B | 1 | 177753776/177936525 | 2.82E-04 | rs633715 (177852580) | AfA | rs75552107 | 177925677 | G | 0.158 | 0.127 | 0.04 | 6.85E-04 | 0.891 | 18599 |
| H/L | rs78368018 | 177777983 | A | 0.003 | -0.825 | 0.21 | 9.42E-05 | 0.038 | 12787 | ||||||
| AsA | rs7518576 | 177849963 | T | 0.459 | 0.081 | 0.03 | 1.19E-03 | 0.885 | 8265 | ||||||
| TE** | rs604388 | 177877979 | C | 0.427 | -0.060 | 0.01 | 3.39E-05 | - | 31349 | ||||||
| [20] | BDNF | 11 | 27452706/ 27749725 | 2.48E-04 | rs7103411 (27700125) | AfA | rs113940328 | 27530168 | C | 0.053 | 0.140 | 0.04 | 2.31E-04 | 0.510 | 20209 |
| H/L | rs11030104 | 27684517 | G | 0.173 | 0.076 | 0.03 | 5.04E-03 | 0.851 | 15346 | ||||||
| AsA | rs1491850 | 27749725 | C | 0.412 | 0.073 | 0.02 | 3.38E-03 | 0.933 | 8273 | ||||||
| TE** | rs4923463 | 27672500 | G | 0.177 | 0.068 | 0.02 | 3.54E-05 | - | 43824 | ||||||
| [13] | FTO | 16 | 53539509/ 54185787 | 8.98E-05 | rs9939609 (53820527) | AfA | rs76299885 | 53950231 | A | 0.136 | -0.119 | 0.04 | 3.48E-03 | 0.483 | 19545 |
| H/L | rs112372930 | 53898024 | A | 0.017 | 0.325 | 0.09 | 5.28E-04 | 0.112 | 13527 | ||||||
| AsA | rs150356630 | 53830590 | T | 0.075 | -0.198 | 0.05 | 1.43E-04 | 0.864 | 8273 | ||||||
| TE** | rs11642841 | 53845487 | A | 0.149 | -0.073 | 0.02 | 2.07E-05 | - | 43797 |
*Bonferroni correction for the number of SNPs r2<0.2 in region in MetaboChip data from the ARIC African Americans (n = 1419 males, n = 2332 females), using a 50-SNP window and shifting the window in each iteration by 5 SNPs.
**Strongest SNP marker in modified random-effects trans-ethnic meta-analysis across three race/ethnic groups (African, Hispanic/Latina, and Asian Americans).
Significant SNP-associations below specific Bonferroni p-values for a given locus are shown in bold.
Nominally significant heterogeneity p-values (p<0.05) shown in italics.
Trans-ethnic P-value represented a modified Han and Eskin p-value.
All SNPs are oriented on positive strand and positions based on Build 37.
Abbreviations: AfA = African American, AsA = Asian American, BP = Base pair, Chr = Chromosome, Freq = Frequency for coded decreasing allele, GWAS = Genome-wide association study, H/L = Hispanic/Latina, Pop = Racial/ethnic group or trans-ethnic analysis, TE = Trans-ethnic modified random effects, MA = Minor Allele, N = Sample Size, Ref = Reference, SE = Standard Error, SNP = Single nucleotide polymorphism.