rs1042725

badMag 3.5

This is a 3 prime utr variant variant in the HMGA2 gene.

Key Literature Trait Associations

Height

One of the strongest common variants associated with adult height. Located in the 3'UTR of HMGA2, a chromatin architectural factor involved in growth. Each C allele adds approximately 0.3 cm to predicted height, though individual height is influenced by hundreds of variants plus environment.

Weedon MN et al. “A common variant of HMGA2 is associated with adult and childhood height in the general population.” Nature Genetics 39(10):1245-50 (2007)

Allele C

OR —

β 0.400

p 4.0e-16

N 34,019

Large GWAS

European

Lettre G et al. “Identification of ten loci associated with height highlights new biological pathways in human growth.” Nature Genetics 40(5):584-591 (2008)

Allele C

OR —

β 0.300

p 1.0e-30

Large GWAS

Yang TL et al. “HMGA2 is confirmed to be associated with human adult height.” Annals of Human Genetics (2010)

Allele C

OR —

p 4.3e-9

N 11,021

Large GWAS

European and East Asian

Bouatia-Naji N et al. “Smallness for gestational age interacts with high mobility group A2 gene genetic variation to modulate height.” European Journal of Endocrinology (2009)

Allele C

OR —

β 0.940

p 9.0e-3

N 6,113

Preliminary work

European (French)

“Variations in the high-mobility group-A2 gene (HMGA2) are associated with idiopathic short stature”

Allele C

OR 1.51

p —

N 473

Candidate gene study

European (Italian)

Birth weight

The T allele of rs1042725 is associated with lower birth weight (beta ≈ −0.047 units, p=1×10⁻¹⁹) in large-scale GWAS meta-analyses of fetal growth traits. This is consistent with HMGA2's known role in fetal growth regulation, as HMGA2 knockout mice exhibit a proportionate dwarf phenotype. The association adds to evidence that rs1042725 influences fetal growth trajectories, not only postnatal height, and parallels findings for infant head circumference at the same locus.

Horikoshi M et al. “Genome-wide associations for birth weight and correlations with adult disease.” Nature 538(7624):248-252 (2016)

Allele T

OR —

β -0.047 ±0.005

p 1.0e-19

N 153,781

Large GWAS

multi-ancestry

Head circumference

The T allele of rs1042725 is genome-wide significantly associated with smaller infant head circumference (beta = −0.065 SD, p=2.8×10⁻¹⁰) in a large study of over 29,000 European-ancestry infants. Notably, this effect on head circumference was largely independent of height, suggesting a distinct neurodevelopmental or cranial growth mechanism beyond HMGA2's general role in linear growth. This locus at 12q15 was one of only two loci identified at genome-wide significance for infant head circumference in the discovery meta-analysis.

Taal HR et al. “Common variants at 12q15 and 12q24 are associated with infant head circumference.” Nature Genetics 44(5):532-538 (2012)

Allele T

OR —

β -0.065

p 2.8e-10

N 29,857

Large GWAS

European

Bone mineral density

The minor (T) allele of rs1042725 has been associated with decreased tibia trabecular volumetric bone mineral density in two independent cohorts of men (Afro-Caribbean p=0.007; Caucasian p=0.0007), suggesting HMGA2 may influence bone density independently of its height effect. The association was observed without a concurrent height effect in these male cohorts, which is notable given that height and BMD are often correlated. Evidence is limited to a single study with moderate sample size and has not been replicated in large-scale BMD GWAS to date.

“Association of a high mobility group gene (HMGA2) variant with bone mineral density”

Allele T

OR —

p 7.0e-4

N 3,228

Preliminary work

Afro-Caribbean and European American

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GWAS Catalog Trait Associations (14)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

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Research that mentions this SNP (2)

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Genome-wide association scan for stature in Chinese: evidence for ethnic specific loci

AssociationN=3,571Shu-Feng Lei et al.(2009)· Human Genetics

Genome-wide association study in 618 Northern Chinese and replication in 2,953 Southern Chinese identified 13 contiguous SNPs in the ZNF510/ZNF782 region significantly associated with stature (P = 9.71×10^-5 to 3.11×10^-6, FDR q = 0.036-0.046). The most significant SNP rs10816533 replicated in Southern Chinese (P = 0.029, combined P = 1.55×10^-6), suggesting this is an ethnic-specific locus for height variation in Chinese populations.

Traits studied:Adult heightHuman stature

PubMed DOI Metascience Observatory

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Uterine leiomyomata and decreased height: a common HMGA2 predisposition allele

AssociationN=248Jennelle C. Hodge et al.(2009)· Human Genetics

This family-based candidate gene study identified a TC227 dinucleotide repeat (27 TC repeats) in the 5' UTR of HMGA2 significantly associated with uterine leiomyomata predisposition (p = 0.00005) and decreased height (p = 0.0021) in 248 White sister-pair families. TC227-positive women were on average 1.5 cm shorter than non-carriers. Expression analysis showed a trend toward higher HMGA2 expression in fibroid tissue from TC227 carriers, and the authors propose TC227 may influence both phenotypes through effects on age of menarche.

rs1042725

Key Literature Trait Associations

Height

Birth weight

Head circumference

Bone mineral density

GWAS Catalog Trait Associations (14)

Research that mentions this SNP (2)

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