Table 8.
Significantly associated haplotype regions (global P < 0.05) with HDL-C and ApoA-I
| Region # | Trait | Consecutive Significantly Associated Haplotype Windows (global P < 0.05) | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Haplotype Windows # | Chr12 Positiona | The Composited Variants in the Region, 5′ to 3′ Direction | Most Relevant Haplotype | ||||||
| (Location) | |||||||||
| Start (5′) | End (3′) | SNP Nameb-SNP IDc/Chr12 Positiona | Major/Minor Alleles | Haplotype # | Sequence | β (Min-Max) | |||
| 1 | HDL-C | 44 | 125300551 | 125299542 | p48969-rs2343394 | C/T | h44.3 | CCWGCGG | 0.4910–1.0491 |
| 45 | (intron 2) | (exon 3) | p49537-rs7305310 | C/T | h45.2 | ||||
| 46 | p49570delC-rs145376237 | W/D | h46.2 | ||||||
| 47 | p49690-rs4765615 | G/A | hap.base47 | ||||||
| p49759-rs146272788 | C/T | hap.base44 | CCWACGG | −0.4701 | |||||
| p49978-rs5891 (p.Val135Ile) | G/A | hap.base45 | |||||||
| p50024-rs368880622 | G/T | hap.base46 | |||||||
| h47.1 | |||||||||
| 2 | ApoA-I | 47 | 125299830 | 125299369 | p49690-rs4765615 | G/A | h47.1 | ACGGTT | (−0.8907)–3.3792 |
| 48 | (intron 2) | (intron 3) | p49759-rs146272788 | C/T | h48.1 | ||||
| 49 | p49978-rs5891 (p.Val135Ile) | G/A | h49.1 | ||||||
| p50024-rs368880622 | G/T | ||||||||
| p50118-rs58710319 | C/T | ||||||||
| p50151-rs2278986 | T/C | ||||||||
| 3 | ApoA-I | 70 | 125294893 | 125292516 | p54627-chr12_125294893 | G/C | h70.2 | GCGTAG | 2.0304–2.1103 |
| 71 | (intron 5) | (intron 6) | p54856-chr12_125294664d | C/T | h71.3 | ||||
| 72 | p55923-rs838900 | G/A | h72.3 | ||||||
| p55963-rs7134858 | C/T | ||||||||
| p56845-rs838902 | A/G | ||||||||
| p57004-rs187562853 | G/A | ||||||||
| 4 | ApoA-I | 78 | 125291928 | 125286037 | p57592-rs838903 | G/A | h78.5 | GTTTCGCTG | 4.7307–5.5715 |
| 79 | (intron 7) | (intron 7) | p58514-rs838905 | T/C | h79.6 | ||||
| 80 | p58664-rs865716 | A/T | h80.6 | ||||||
| 81 | p60255-rs3782287 | C/T | hap.base81 | ||||||
| 82 | p61872-rs838909 | C/T | hap.base82 | ||||||
| 83 | p62140-rs838910 | G/T | hap.base83 | ||||||
| p62409-rs838911 | C/T | h78.2 | GTACCTCTG | 0.6384–3.8641 | |||||
| p62615-rs7138386 | T/C | h79.2 | |||||||
| p63483-rs838912 | G/A | hap.base80 | |||||||
| h81.3 | |||||||||
| h82.2 | |||||||||
| h83.4 | |||||||||
| 5 | ApoA-I | 95 | 125277653 | 125272763 | p71867-rs7954022 | C/T | h95.5 | CGTTCT | 4.2363-4.7525 |
| 96 | (intron 9) | (intron 9) | p72197-rs838861 | A/G | h96.5 | ||||
| 97 | p72777-rs838862 | C/T | h97.4 | ||||||
| p75766-rs838866 | T/C | ||||||||
| p75778-rs7301120 | C/T | ||||||||
| p76757-rs9919713 | A/T | ||||||||
| 6* | ApoA-I | 109 | 125271118 | 125269475 | p78402-rs838898 | G/A | h109.6 | GCCTGCA | (−3.3720)─(−1.8104) |
| 110 | (intron 10) | (intron 11) | p78430-rs838897 | C/G | h110.6 | ||||
| 111 | p78747-rs2293440 | T/C | h111.2 | ||||||
| 112 | p78791-rs75289200 | T/C | h112.3 | ||||||
| p79721-rs838896 | G/C | ||||||||
| p79828-rs838895 | C/G | ||||||||
| p80045-rs838893 | G/A | ||||||||
| 7* | HDL-C | 111 | 125270773 | 125267501 | p78747-rs2293440 | T/C | h111.4 | TTGGAGC | 0.3755–2.3949 |
| 112 | (intron 11) | (intron 11) | p78791-rs75289200 | T/C | h112.2 | ||||
| 113 | p79721-rs838896 | G/C | h113.1 | ||||||
| 114 | p79828-rs838895 | C/G | h114.1 | ||||||
| p80045-rs838893 | G/A | ||||||||
| p81863-rs185445624 | G/A | ||||||||
| p82019-rs838890 | C/T | ||||||||
| 8 | HDL-C | 117 | 125267501 | 125267086 | p82019-rs838890 | C/T | h117.2 | TCGGC | (−1.0134)–(−0.9657) |
| 118 | (intron 11) | (intron 12) | p82264-rs141545424 (p.Gly501Gly)d | C/A | h118.2 | ||||
| p82340-rs77483223 | G/A | ||||||||
| p82369-rs75446635 | G/A | ||||||||
| p82434-rs838889 | T/C | ||||||||
| 9 | HDL-C | 123 | 125265636 | 125262553 | p83884-rs701106 | C/T | h123.4 | CCCTGA | (−1.180)–(−0.2329) |
| 124 | (intron 12) | (exon 13-3′ UTR) | p86245-rs188375019 | C/T | h124.2 | ||||
| 125 | p86276-rs747155 | C/T | h125.2 | ||||||
| p86316-rs701104 | G/T | ||||||||
| p86481-rs701103 (p.Gly499Arg, isoform 2) | G/A | ||||||||
| p86967-rs187492239 | A/G | ||||||||
ApoA-I apolipoprotein A-I, del/D deletion, HDL-C high-density lipoprotein cholesterol, SNP single nucleotide polymorphism, UTR untranslated region, W wild type allele for deletion on the RefSeq
All alleles on the reverse strand. HDL-C and ApoA-I variables were in mg/dL and Box-Cox transformed
Results were adjusted for covariates: sex, age, waist, current smoking (yes/no), and minutes of daily walking or biking to work (jobmin) for HDL-C; sex and age for ApoA-I
All nine haplotype regions are shown in Fig. 3
Detailed single-site associations are shown in Additional file 14: Table S9 and Additional file 15: Table S10
Detailed haplotype associations are shown in Table 7 and Additional file 16: Table S11
Regions with asterisk (*) indicate regions that included the haplotype window exhibiting the most significant association signal (the smallest global P) for the associated trait
For each region, the most significant associated haplotype window is shown in bold
SNPs with significant evidence of association with the same trait in both single-site and haplotype analyses (single-site P < 0.05 and global P < 0.05) are shown in bold
SNPs with significant evidence of association with different trait in single-site and haplotype analyses (single-site P < 0.05 and global P < 0.05) are shown in italic bold
a, bRefSeq of SCARB1: hg19, NM_005505 (CHIP Bioinformatics)
cdbSNP build 139: GRCh37.p10
dRare variants of interest with potential effects on lipid traits; see details in Table 6