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https://sq-96.github.io/multigroup_ctwas_analysis/realdata_final_multigroup_summary.html

LDL-ukb-d-30780_irnt

New genes identified by multi-group

LDLR, PCSK9, CETP, CCNJ, PKN3, ABCA8, FCGRT, DNAJC13, LRCH4, HMGCR, ASGR1, APOB, ADH1B, FLT3, ZDHHC18, USP39, TIMD4, ZFYVE1, ACP6, NPC1L1, ERGIC3, MITF, PSRC1, SNX17, GABBR1, HMGN1, KIF13B, R3HDM2, MYPOP, SIPA1, USP3, PGS1, FAM117B, ADRB1, PHC1, WASHC4, TPD52, THOP1, ZFP28, DMTN, PDE4C, XPNPEP3

Genes with Strong Evidence of Association with LDL Cholesterol

LDLR (Low-Density Lipoprotein Receptor): Mutations in LDLR are a primary cause of familial hypercholesterolemia, leading to elevated LDL cholesterol levels due to impaired clearance of LDL particles from the bloodstream.

PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9): PCSK9 regulates LDL receptor degradation. Gain-of-function mutations increase LDL cholesterol levels, while loss-of-function mutations are associated with reduced LDL cholesterol and a lower risk of coronary heart disease.

APOB (Apolipoprotein B): APOB encodes the primary protein component of LDL particles. Mutations can impair LDL binding to its receptor, resulting in elevated LDL cholesterol levels.

CETP (Cholesteryl Ester Transfer Protein): CETP facilitates the transfer of cholesteryl esters from HDL to LDL and VLDL particles. Variants in CETP can influence HDL and LDL cholesterol levels.

HMGCR (3-Hydroxy-3-Methylglutaryl-CoA Reductase): This enzyme is the rate-limiting step in cholesterol biosynthesis and is the target of statin therapy. Variants in HMGCR can affect LDL cholesterol levels.

NPC1L1 (Niemann-Pick C1-Like 1): NPC1L1 is critical for intestinal cholesterol absorption. Inhibitors like ezetimibe target this protein to reduce LDL cholesterol levels.

ASGR1 (Asialoglycoprotein Receptor 1): Loss-of-function mutations in ASGR1 have been associated with reduced LDL cholesterol levels and a lower risk of coronary artery disease.

PSRC1 (Proline and Serine Rich Coiled-Coil 1): Variants near PSRC1 have been linked to LDL cholesterol levels in genome-wide association studies (GWAS).

TIMD4 (T-cell Immunoglobulin and Mucin Domain Containing 4): Variants in TIMD4 have been associated with decreased serum triglyceride levels and a reduced risk of coronary heart disease and ischemic stroke in certain populations.

Genes reported by single eQTL analysis but not by multi-group analysis

PARP9，DDX56，MZF1，CLDN23，FUT2，VIL1，KLHDC7A，WBP1L

Genes with No Strong or Established Evidence for LDL Association

DDX56 RNA helicase with roles in ribosome biogenesis; no known links to lipid metabolism or LDL levels.

MZF1 A transcription factor; not directly linked to lipid or cholesterol traits.

VIL1 Villin 1, an actin-binding protein in the intestinal brush border; no direct LDL link known.

WBP1L Not currently known to be involved in lipid metabolism or LDL levels.

IBD-ebi-a-GCST004131

New genes identified by multi-group

HLA-DQB1, BRD7, PTPN2, FOSL2, ERI3, CD244, ADAM15, TNFRSF6B, IP6K2, FCGR2A, SBNO2, GPR35, SMAD3, MAST2, ACBD3, STAT3, CASC3, RORC, RGS14, ATG16L1, AUH

Genes with Evidence of Association with IBD

HLA-DQB1 – Involved in antigen presentation via MHC class II; variants strongly associated with IBD due to dysregulated immune recognition of gut antigens.

PTPN2 – Negatively regulates pro-inflammatory JAK/STAT signaling; loss-of-function variants increase intestinal inflammation and are linked to Crohn’s disease and ulcerative colitis.

CD244 – Modulates NK and T cell cytotoxic responses; may contribute to abnormal immune cell activation and mucosal inflammation in IBD.

ADAM15 – Promotes leukocyte transmigration and epithelial barrier remodeling; upregulated in inflamed IBD tissues.

TNFRSF6B – A decoy receptor blocking FasL-induced apoptosis; implicated in disrupted immune homeostasis and epithelial cell survival in IBD.

FCGR2A – Mediates phagocytosis and clearance of immune complexes; genetic variants are associated with dysregulated innate immune responses in IBD.

GPR35 – G protein-coupled receptor expressed in intestinal immune cells; risk allele linked to reduced epithelial repair and altered immune cell migration in IBD.

SMAD3 – Mediates TGF-β signaling involved in immune tolerance and epithelial regeneration; implicated in intestinal fibrosis and chronic inflammation in IBD.

STAT3 – Transduces IL-6 and IL-23 signals; critical for Th17 cell differentiation and intestinal barrier function. Hyperactivation promotes chronic intestinal inflammation.

RORC – Encodes RORγt, the master regulator of Th17 cells; promotes IL-17-mediated mucosal inflammation in IBD.

ATG16L1 – Essential for autophagy in intestinal epithelial cells and Paneth cells; risk variants impair bacterial clearance and epithelial homeostasis in Crohn’s disease.

SBP-ukb-a-360

New genes identified by multi-group

BAG6, PKN2, PKP4, ENPEP, FES, RERE, NUDT5, RAB34, SLC9A3R2, TMBIM1, HOXA11, DMWD, UVSSA, TMEM175, MTMR9, ADH1B, SP140L, PPP3R1, NAA60, CCDC163, FHOD3, SGSM3, NPR1, PAQR5, CLCN6, THAP3, CAMK1D, TBX2, FBXO38, REXO1

Genes with Evidence of Association with systolic blood pressure

ENPEP: A GWAS in East Asians identified genome-wide significant SBP associations at the ENPEP locus. Kidney transcriptome and protein-level Mendelian randomisation linked genetically predicted ENPEP expression to elevated SBP/DBP/PP

NPR1 Rare/low-frequency coding variants show association with SBP in >300k sample-size meta-analyses. It encodes the receptor for atrial/brain natriuretic peptides, central in blood volume and BP regulation

FES A TWAS reported inverse association between predicted FES expression in vascular tissues and SBP