Table 1.
CP associations in the literature
| Type | Locus | Phenotypes | Result | Refs |
|---|---|---|---|---|
| SNP (same direction of risk) | rs11209026 (IL23R) | Crohn’s disease, ankylosing spondylitis, ulcerative colitis, psoriasis | The minor allele (A) of rs11209026 is protective for Crohn’s disease, ankylosing spondylitis, ulcerative colitis and psoriasis | 125–128 |
| SNP (same direction of risk) | rs6983267 (8q24) | Prostate and colorectal cancer | The G allele increases risk for prostate cancer and colorectal cancer | 23,24 |
| SNP (different direction of risk) | rs12720356 (TYK2) | Crohn’s disease and psoriasis | The G allele increases risk for Crohn’s disease and decreases risk for psoriasis | 128,129 |
| Gene (different SNPs) | DNAH11 | LDL cholesterol and multiple myeloma | rs12670798 is associated with LDL cholesterol and rs4487645 is associated with multiple myeloma | 130,131 |
| Gene (different SNPs) | FTO | BMI and melanoma | rs8050136 is associated with body mass index and rs16953002 is associated with melanoma | 17,18 |
| Region (different SNPs) | 9q21.3 | Coronary artery disease, glioma, intracranial aneurysm | rs4977574 is associatied with coronary artery disease, rs4977756 with glioma, rs1333040 with intracranial aneurysm | 19–22 |
| Copy number variation | 16p2.11 duplication | Schizophrenia, autism, intellectual disability, developmental delay, congenital malformations | CNV duplication increases risk for all five disorders | 26 |
| Copy number variation | 7q11.23 | Autism and Williams–Beuren syndrome | CNV deletion causes Williams–Beuren syndrome and de novo CNV duplication increases risk for autism | 132,133 |
| Pathway | Immune cell signalling | Autoimmune thyroid disease, coeliac disease, Crohn’s disease, rheumatoid arthritis, systemic lupus erythematosus, T1D | Genes in this pathway have been implicated across six diseases | 34 |
| Polygenic scores | – | Schizophrenia and bipolar disorder | Schizophrenia and bipolar disorder share genetic factors that increase risk to both disorders | 28 |
| Genetic correlation | – | T2D and hypertension | Positive genetic correlation between T2D and hypertension suggests that shared genetic factors increase risk for both traits | 41 |
BMI, body mass index; CNV, copy number variant; CP, cross-phenotype; DNAH11, dynein, axonemal, heavy chain 11; FTO, fat mass and obesity associated; IL23R, interleukin 23 receptor; LDL, low-density lipoprotein; SNP, single-nucleotide polymorphism; T1D, type 1 diabetes; T2D, type 2 diabetes; TYK2, tyrosine kinase 2. This table provides some examples of different types of observed CP effects. These are illustrative examples and are not exhaustive; many additional CP associations have been published.