rs7498665

This is a variant in the SH2B1 gene that changes a threonine to an alanine.

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GWAS Catalog Trait Associations (10)

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

body mass index

Pulit SL et al. “Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry.” Human Molecular Genetics 28(1):166-174 (2019)
Allele G
OR 0.03
p 1.0e-66
N 806,834
Meta-analysisLarge GWAS
European
Sidorenko J et al. “Genetic architecture reconciles linkage and association studies of complex traits.” Nature Genetics 56(11):2352-2360 (2024)
Allele G
OR 0.03
p 2.0e-52
N 650,000
Large GWAS
European
Hawkes G et al. “Genetic evidence that high BMI in childhood has a protective effect on intermediate diabetes traits, including measures of insulin sensitivity and secretion, after accounting for BMI in adulthood.” Diabetologia 66(8):1472-1480 (2023)
Allele G
OR 0.03
p 6.0e-40
N 441,761
Large GWAS
European
Thorleifsson G et al. “Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity.” Nature Genetics 41(1):18-24 (2009)
Allele G
OR 3.63
p 3.0e-10
N 73,758
Large GWAS
multi-ancestry
Willer CJ et al. “Six new loci associated with body mass index highlight a neuronal influence on body weight regulation.” Nature Genetics 41(1):25-34 (2009)
Allele G
OR 0.15
p 5.0e-11
N 32,387
Large GWAS
European

fat pad mass

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)
Allele G
OR 0.03
p 2.0e-50
N 394,642
Large GWAS
European

body fat percentage

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)
Allele G
OR 0.02
p 1.0e-47
N 394,642
Large GWAS
European

waist circumference

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)
Allele G
OR 0.02
p 5.0e-40
N 394,642
Large GWAS
European
Shungin D et al. “New genetic loci link adipose and insulin biology to body fat distribution.” Nature 518(7538):187-196 (2015)
Allele G
OR 0.03
p 1.0e-22
N 143,480
Large GWAS
multi-ancestry

body height

Richardson TG et al. “Use of genetic variation to separate the effects of early and later life adiposity on disease risk: mendelian randomisation study.” Bmj (clinical Research Ed.) 369:m1203 (2020)
Allele A
OR 0.02
p 6.0e-35
N 453,169
Large GWAS
European

visceral adipose tissue quantity

Karlsson T et al. “Contribution of genetics to visceral adiposity and its relation to cardiovascular and metabolic disease.” Nature Medicine 25(9):1390-1395 (2019)
Allele G
OR 0.03
p 2.0e-26
N 325,153
Large GWAS
European

waist-hip ratio

Pulit SL et al. “Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry.” Human Molecular Genetics 28(1):166-174 (2019)
Allele A
OR 0.02
p 1.0e-22
N 381,152
Meta-analysisLarge GWAS
European

obesity

Berndt SI et al. “Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture.” Nature Genetics 45(5):501-12 (2013)
Allele G
OR 1.07
p 3.0e-13
N 204,498
Meta-analysisLarge GWAS
European

body weight

Thorleifsson G et al. “Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity.” Nature Genetics 41(1):18-24 (2009)
Allele G
OR 3.69
p 1.0e-9
N 73,758
Large GWAS
multi-ancestry

serum alanine aminotransferase amount

Ghouse J et al. “Integrative common and rare variant analyses provide insights into the genetic architecture of liver cirrhosis.” Nature Genetics 56(5):827-837 (2024)
Allele G
OR 0.00
p 4.0e-8
N 1,010,710
Large GWAS
European
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ClinVar annotation

Benign★★★☆
3 submitters2 publications
View on ClinVar →
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Research that mentions this SNP (5)

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Genetic variation of FTO: rs1421085 T&gt;C, rs8057044 G&gt;A, rs9939609 T&gt;A, and copy number (CNV) in Mexican Mayan school‐aged children with obesity/overweight and with normal weight
ReviewLizbeth González‐Herrera et al.(2019)· American Journal of Human Biology

A literature review of 70 studies examining single nucleotide polymorphisms (SNPs) associated with obesity in Mexican populations published 2011-2021. The authors identified SNPs with differential behavior in Mexican compared to Caucasian populations, including rs17782313 (MC4R), rs6548238 (TMEM18), rs6265 (BDNF), rs7498665 (SH2B1), and notably rs6232 (PCSK1) associated with early-onset obesity in Mexican youth. The review emphasizes ethnicity-dependent genetic effects on BMI heritability (40-70%) and highlights genes involved in cholesterol metabolism and adipokine signaling pathways.

Traits studied:AdiposityBlood pressureBody mass index (BMI)Cardiovascular risk factorsDyslipidemiaInsulin resistanceMetabolic syndromeObesityOverweightType 2 diabetes
PubMedDOIMetascience Observatory
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Common variants in BDNF, FAIM2, FTO, MC4R, NEGR1, and SH2B1 show association with obesity‐related variables in Spanish Roma population
AssociationN=3,210Alaitz Poveda et al.(2014)· American Journal of Human Biology

This study performed fine mapping of the obesity-associated region chr16p11.2 by screening the coding regions of APOBR, SULT1A1, SULT1A2, and TUFM genes in 95 extremely obese children and adolescents. Two APOBR variants, rs180743 (p.Pro428Ala) and rs3833080 (p.Gly369_Asp370del9), showed significant association with obesity (p=0.002 and p=0.003 respectively) in case-control analysis of 1,873 obese cases versus 435 lean controls, with odds ratios of 1.27 and 1.25 per allele.

Traits studied:Body mass indexExtreme obesityObesity
PubMedDOIMetascience Observatory
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Associations of polymorphisms in the genes of FGFR2, FGF1, and RBFOX2 with breast cancer risk by estrogen/progesterone receptor status
AssociationN=2,416Yu‐Ling Cen et al.(2013)· Molecular Carcinogenesis

A hospital-based case-control study in rural and urban India (1,204 cases; 1,212 controls) examined genetic and lifestyle risk factors for breast cancer. Four SNPs in FGFR2 (rs1219648, rs2420946, rs2981575, rs2981582) showed positive associations with breast cancer (ORs 1.32-1.47). Additional SNPs in obesity and metabolic genes (rs374748 in FBN2, rs2922763 in HNF4G, rs2116830 in KCNMA1, rs11121832 in MTHFR, rs16886165 in MAP3K1, rs11594610 in TCF7L2, rs2274459 in MLN) were associated with increased breast cancer risk. Waist-to-hip ratio ≥0.95 showed strong association (OR 3.78; 95% CI 2.92-4.89), and women living first 20 years in rural areas showed protective effect (OR 0.77).

Traits studied:Breast cancerBreast cancer riskER+/PR+ breast cancerER/PR negative breast cancerTriple negative breast cancer
PubMedDOIMetascience Observatory
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Common variants near BDNF and SH2B1 show nominal evidence of association with snacking behavior in European populations
AssociationN=14,000Sébastien Robiou-du-Pont et al.(2013)· Journal of Molecular Medicine

Genome-wide association study examining common variants near BDNF (rs6265, rs925946) and SH2B1 (rs7498665) in relation to snacking behavior across three European cohorts (French obese children, Swiss obese, D.E.S.I.R.). The study reports nominal evidence of association, with rs925946 in BDNF showing OR=1.21 (p=5.03×10⁻³) in the D.E.S.I.R. cohort and rs7498665 in SH2B1 showing OR=1.17 (p=9.57×10⁻³) in the Swiss cohort.

Traits studied:ObesitySnacking behavior
PubMedDOIMetascience Observatory
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Is the thrifty genotype hypothesis supported by evidence based on confirmed type 2 diabetes- and obesity-susceptibility variants?
AssociationSoutham L et al.(2009)· Diabetologia

This study tests the thrifty genotype hypothesis by examining 17 confirmed type 2 diabetes susceptibility loci and 13 obesity-susceptibility loci for signatures of positive selection. Using ancestral/derived allele analysis, integrated haplotype scores (iHS), and population differentiation (FST), the authors found limited evidence supporting the thrifty genotype hypothesis. Only rs7901695 at TCF7L2 showed notably elevated FST values (0.579 between JPT+CHB and YRI populations), and FTO showed the strongest selection signal among obesity loci (iHS=1.991).

Traits studied:Body mass index (BMI)ObesityType 2 diabetes
PubMedDOIMetascience Observatory

About SH2B1

This gene encodes a member of the SH2-domain containing mediators family. The encoded protein mediates activation of various kinases and may function in cytokine and growth factor receptor signaling and cellular transformation. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2009]

View all SH2B1 variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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