Table 1  Phenotypic Overlap between Rare and Complex Disorders
Gene: Associated Rare Disease   Reference SNP: Complex Disease   Common HPO Terms
CD247: immunodeficiency due to defect in CD3-ζ (MIM: 610163)  rs840016: rheumatoid arthritis59  edema (HP: 0000969),arthralgia (HP: 0002829),arthritis (HP: 0001369),autoimmunity (HP: 0002960)
FSHR: ovarian hyperstimulation syndrome (MIM: 608115) and ovarian dysgenesis 1 (MIM: 233300)  rs2268361: polycystic ovary syndrome60  abnormality of the ovary (HP: 0000137),decreased fertility (HP: 0000144),primary amenorrhea (HP: 0000786)
PPARG: lipodystrophy, familial partial, type 3 (MIM: 604367)  rs13081389: type 2 diabetes mellitus61  hyperglycemia (HP: 0003074),hyperinsulinemia (HP: 0000842),hypertension (HP: 0000822)
LPL: type I hyperlipoproteinemia (MIM: 238600)  rs295: metabolic syndrome X62  hypercholesterolemia (HP: 0003124),hyperlipoproteinemia (HP: 0010980),coronary artery disease (HP: 0001677),pancreatitis (HP: 0001733)
LRRK2: Parkinson disease 8 (MIM: 607060)  rs34778348: Parkinson disease63  rigidity (HP: 0002063),bradykinesia (HP: 0002067),dementia (HP: 0000726),resting tremor (HP: 0002322)
HCN4: sick sinus syndrome 2 (MIM: 163800)  rs7164883: atrial fibrillation  arrhythmia (HP: 0011675),tachycardia (HP: 0001649),sinus brachycardia (HP: 0001688)
HYDIN: ciliary dyskinesia, primary, 5 (MIM: 608647)  rs12149070: COPD64  respiratory tract infection (HP: 0011947),respiratory insufficiency (HP: 0002093),bronchiectasis (HP: 0011947)
GWAS hits localized in the vicinity of Mendelian-disease-associated genes could be associated with common diseases that have phenotypic overlaps with the corresponding Mendelian diseases. Seven examples in which common and rare diseases linked to neighboring loci and showed substantial phenotypic overlap were manually chosen. The protein-coding gene associated with the rare disease, as well as the accession number of the polymorphism located in non-coding sequence near the gene, is shown. The following abbreviation is used: COPD, chronic obstructive pulmonary disease.