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
▶

GWAS Catalog Trait Associations (14)

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

birth weight

Yang XL et al. “Three Novel Loci for Infant Head Circumference Identified by a Joint Association Analysis.” Frontiers in Genetics 10:947 (2019)
Allele T
OR 0.04
p 2.0e-33
N 182,902
Large GWAS
European
Horikoshi M et al. “New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.” Nature Genetics 45(1):76-82 (2013)
Allele T
OR 0.05
p 1.0e-19
N 26,836
Large GWAS
European

body height at birth

Yang XL et al. “Three Novel Loci for Infant Head Circumference Identified by a Joint Association Analysis.” Frontiers in Genetics 10:947 (2019)
Allele T
OR 0.07
p 2.0e-29
N 182,902
Large GWAS
European

sex hormone-binding globulin measurement

Ruth KS et al. “Using human genetics to understand the disease impacts of testosterone in men and women.” Nature Medicine 26(2):252-258 (2020)
Allele C
OR 0.01
p 8.0e-25
N 368,929
Large GWAS
European

head circumference

Yang XL et al. “Three Novel Loci for Infant Head Circumference Identified by a Joint Association Analysis.” Frontiers in Genetics 10:947 (2019)
Allele T
OR 0.10
p 9.0e-22
N 182,902
Large GWAS
European
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 0.07
p 3.0e-10
N 10,768
Large GWAS
European

body height

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 T
OR 0.48
p 3.0e-20
N 15,821
Large GWAS
European
Weedon MN et al. “Genome-wide association analysis identifies 20 loci that influence adult height.” Nature Genetics 40(5):575-83 (2008)
Allele T
OR 0.05
p 3.0e-18
N 13,665
Large GWAS
European
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 T
OR 0.40
p 6.0e-16
N 4,921
Large GWAS
European

appendicular lean mass

Hernandez Cordero AI et al. “Genome-wide Associations Reveal Human-Mouse Genetic Convergence and Modifiers of Myogenesis, CPNE1 and STC2.” American Journal of Human Genetics 105(6):1222-1236 (2019)
Allele T
OR 0.05
p 1.0e-14
N 181,862
Large GWAS
European

type 2 diabetes mellitus

Mahajan A et al. “Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps.” Nature Genetics 50(11):1505-1513 (2018)
Allele T
OR 1.05
p 2.0e-13
N 898,130
Large GWAS
European

free cholesterol to total lipids in medium LDL percentage

Zoodsma M et al. “A genetic map of human metabolism across the allele frequency spectrum.” Nature Genetics 57(10):2445-2455 (2025)
Allele T
OR 0.01
p 1.0e-11
N 450,015
Large GWAS
multi-ancestry

neutrophil count

Chen MH et al. “Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations.” Cell 182(5):1198-1213.e14 (2020)
Allele T
OR 0.01
p 3.0e-11
N 519,288
Large GWAS
European
▶

Research that mentions this SNP (2)

▶
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
PubMedDOIMetascience Observatory
▶
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.

Traits studied:Age of menarcheHeightUterine leiomyomata
PubMedDOIMetascience Observatory

Gene information from NCBI Gene. Variant classifications from ClinVar.

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