Table 2.
Biological Candidate Genes at Previously Unreported Adiponectin-Associated Loci
| Lead Variant | EAF | Nearest Gene | n Variants r2 ≥ 0.80 (Distance kb) | n Variants r2 ≥ 0.60 (Distance kb) | Function/Nonsynonymous Variants (r2 > 0.8) | Adipose eQTL Gene (p < 5 × 10−8) | Other Trait Associations (p < 1 × 10−4) | Literature Candidate |
|---|---|---|---|---|---|---|---|---|
| rs2276853 | 0.59 | KIF9 | 330 (597 kb) | 353 (597 kb) | KIF9 (p.Arg638Gly)∗; SETD2 (p.Pro1918His); SCAP (p.Val543Ile); NBEAL2 (p.Arg511Gly); PTPN23 (p.Ala818Thr) | – | WHRadjBMI, adiponectin, T2D | PTH1R |
| rs3087866 | 0.79 | DALRD3 | 73 (819 kb) | 210 (833 kb) | DALRD3 (p.Gln299Arg)∗ | AMT, NICN1, PRKAR2A, QRICH1 | FFMI, WHRadjBMI, Adiponectin, Menarche, T2D | PRKAR2A |
| rs13133548 | 0.49 | FAM13A | 41 (35 kb) | 54 (35 kb) | – | FAM13A | BF%, HC, HDL, WHRadjBMI, Adiponectin, BMI, T2D, TG | FAM13A |
| rs13107325 | 0.05 | SLC39A8 | 3 (51 kb) | 4 (196 kb) | SLC39A8 (p.Ala391Thr)∗ | – | BMI, BF%, DBP, FFMI, HC, HDL, HTN, SBP, WC, WHRadjBMI, Adiponectin, TG | SLC39A8 |
| rs10282707 | 0.38 | SNX13 | 9 (104 kb) | 16 (130 kb) | – | – | HDL, TC | HDAC9 |
| rs3735080 | 0.24 | GIMAP7 | 278 (119 kb) | 294 (146 kb) | GIMAP7 (p.Arg83Cys)∗; GIMAP6 (p.Gly241Ser) | – | DBP, FFMI, HTN, SBP | REPIN1; RARRES2 |
| rs11993554 | 0.10 | OPLAH | 37 (57 kb) | 122 (107 kb) | OPLAH (p.Phe612Phe∗, p.Arg31Gln, p.Val340Ile, p.Ser284Arg); EPPK1 (p.Arg936Trp) | – | WHRadjBMI | MAF1 |
| rs10861661 | 0.23 | RIC8B | 14 (134 kb) | 16 (134 kb) | – | – | WHRadjBMI, HDL, TG, HC | CRY1 |
| rs145119400 | 0.005 | SLC38A8 | 2 (257 kb) | 2 (257 kb) | SLC38A8 (p.Pro57Leu)∗ | – | – | CDH13; MBTPS1 |
Biological candidate genes at each of the loci previously not shown to be association with adiponectin. Number of variants in moderate to strong linkage disequilibrium and the distance spanned obtained using data from 1000 Genomes Phase 3 and build hg19 (LDLink). Nonsynonymous variants noted with an asterisk (∗) are the lead variants identified at each locus. eQTLs were identified in METSIM subcutaneous adipose and/or GTEx subcutaneous or visceral adipose tissues (see Table S15). Other trait associations were identified from available summary statistics from the ADIPOGen, DIAGRAM, GIANT, and GLGC consortia, along with the UK Biobank (see Tables S9–S11). Abbreviations: BMI, body mass index; BF%, body fat percentage; DBP, diastolic blood pressure; FFMI, fat free mass index; HC, hip circumference; HDL, high density lipoprotein cholesterol; HTN, hypertension; Menarche, age at menarche; SBP, systolic blood pressure; WC, waist circumference; WHRadjBMI, waist-hip-ratio adjusted for BMI.