Table 2.

Summary of candidate genes in the 20 loci associated with height

SNP	Candidate or nearest gene(s)	Monogenic syndrome caused by mutation in gene	Knockout mouse phenotype	Detailsa
rs6440003	ZBTB38 (zinc finger and BTB domain-containing protein 38)	—	—	Transcription factor
rs2282978	CDK6 (cyclin-dependent kinase-6)	—	15% smaller embryos	Involved in the control of the cell cycle. Interacts with D-type G1 cyclins.
rs1042725	HMGA2 (high-mobility group A2)	Tall stature, extreme bone and dental overgrowth, and multiple lipomas.	Pygmy mice	Belongs to the nonhistone chromosomal high mobility group (HMG) protein family. HMG proteins function as chromatin architectural factors.
rs6060373	GDF5 (growth differentia- tion factor 5)	Chondrodysplasia (abnormally short and deformed limbs); brachydactyly (short digits) DuPan syndrome; multiple synostoses syndrome.	Homozygous null mutants show skeleton defects, such as reduced or absent limb bones and joints.	Involved in bone formation. Also known as cartilage-derived morphogenetic protein 1.
rs16896068	LCORL (ligand-dependent nuclear receptor corepressor- like protein)	—	—	May act as transcription activator.
rs4549631	LOC387103	—	—	Not known.
rs3791675	EFEMP1 (EGF-containing fibulin-like extracellular matrix protein 1)	Doyne honeycomb retinal dystrophy; no obvious skeletal defects.	Normal phenotype	Extracellular matrix. Belongs to the fibulin family.
rs2814993	C6orf106	—	—	Not known.
rs10512248	PTCH1 (patched homolog 1 (Drosophila))	Gorlin syndrome (basal cell carcinoma); holoprosencephaly.	Homozygous null mice die during embryogenesis, heterozygotes larger than normal, with hind limb defects.	Hedgehog signalling. Acts as a receptor for Sonic hedgehog (SHH), Indian hedgehog (IHH) and Desert hedgehog (DHH).
rs12735613	SPAG1 (sperm associated antigen 17)	—	—	Not known.
rs11107116	SOCS2 (suppressor of cyto- kine signaling 2)	—	Homozygous null mice grow more rapidly. Males are 40% heavier than wild-type littermates; the increase in weight results from general increase in visceral organ weight and long bone length.	SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS2 seems to be a negative regulator in the growth hormone/IGF1 signaling pathway.
rs6854783	HHIP (Hedgehog interacting protein)	—	Ectopic expression in transgenic mice results in severe skeletal defects similar to those observed in IHH mutants.	Hedgehog signaling. Modulates hedgehog signaling through direct interaction with members of the hedgehog family including SHH, IHH and DHH.
rs1390401	ZNF678 (zinc finger protein 678)	—	—	Transcription factor. Belongs to the Krüp- pel C2H2-type zinc-finger protein family by similarity.
rs3116602	DLEU7 (deleted in lympho- cytic leukemia 7)	—	—	Not known.
rs6686842	SCMH1 (sex comb on mid- leg homolog 1)	—	Homozygous null mice present with multiple defects including of skeleton.	Polycomb protein. A constituent of the mammalian Polycomb repressive complexes 1 involved in chromatin modifications.
rs10906982	ADAMTSL3 (ADAMTS-like protein 3)	—	—	Extracellular matrix. Strongly similar to members of the ADAMTS family but lacks metalloprotease and disintegrin-like domains.
rs6724465	IHH (Indian hedgehog)	Brachydactyly; acrocapitofemoral dysplasia (cone-shaped ends of hand and hip bones).	Homozygous null mice show impaired chondrocyte proliferation and maturation, resulting in dwarfism and numerous skeletal abnormalities.	Hedgehog signaling. Intercellular signal essential for a variety of patterning events during development. Binds to the patched (PTCH) receptor.
rs10935120	ANAPC13 (anaphase pro- moting complex subunit 13)	—	—	Cell cycle. Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle—regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle.
rs8041863	ACAN (aggrecan)	Autosomal dominant spondylo- epiphyseal dysplasia type Kimberley, characterized by severe, premature osteoarthritis.	Homozygous mutants are dwarfed at birth.	Extracellular matrix. A member of the aggrecan/versican proteoglycan family. Part of the extracellular matrix in cartilaginous tissue.
rs8099594	DYM (dymeclin)	Autosomal recessive disorder characterized by abnormal skeletal development and mental retardation.	—	May have a role in process of intracellular digestion of proteins or in proteoglycan metabolism.

A candidate gene is listed when monogenic human and/or mouse phenotypes and/or expression results clearly suggest a plausible candidate; otherwise, the nearest gene is given, unless there are no genes within the 500-kb window around the SNP. Information on each gene was obtained from either the OMIM or the Jackson Laboratory websites.

^aDetails are from Uniprot summaries.