A 199,000-person Japanese GWAS more than doubled the number of known genetic risk loci for kidney and urinary stones — 6 of the 14 it found are on this page.
Urolithiasis — kidney and urinary tract stones — is a painful condition with a substantial genetic component: a twin study estimated 56% heritability, and people with a family history face more than double the risk. Despite that, genome-wide studies before 2019 had found only 6 risk loci in total.
A 2019 GWAS in a Japanese population studied 11,130 people with urolithiasis against 187,639 controls at discovery, then replicated in 2,289 more cases and 3,817 more controls. It found 14 significant loci overall — 9 of them newly discovered, more than doubling what was known before this study. This page carries 6 of those 14 loci: in EPB41L2, INMT, PDILT, FTO, BCAS3, and BCAS1.
The study also tested each locus against 16 metabolic, kidney, and electrolyte-related traits using up to 160,000 BioBank Japan samples, and found a genetic split: 10 of the 14 loci associated with kidney- or electrolyte-related traits — plausibly acting through stone crystallization directly — while 4 associated instead with broader metabolic traits like obesity, high triglycerides, or high uric acid. This page's FTO is a well-known metabolic and obesity-related gene, already linked on this site's obesity and waist circumference pages — a plausible fit for that second, metabolic route into stone risk rather than a direct kidney one.
A genetic risk score built from the study's findings put the highest-risk fifth of people at 1.71 to 2.13 times the odds of urolithiasis compared with the lowest-risk fifth, depending on the specific comparison made.
Cao et al. 2025 combined European and East Asian data — 31,715 people with kidney stone disease and 943,655 without — and found 59 susceptibility loci, 13 of them new, with similar effects in both populations. Fine-mapping narrowed 1,612 candidate variants at those loci to 25 likely causal signals, and at one new locus pointed to the gene TRIOBP. A polygenic score built across both populations separated risk clearly: compared with people in the middle fifth, those in the lowest fifth had odds of 0.57 (0.51 to 0.63) and those in the highest 1.83 (1.68 to 1.98) — and people with higher scores tended to be younger when their stones first appeared.
Two of this page's variants come from that study: rs10051765, between RGS14 and SLC34A1 (odds ratio 0.88 per copy of the T allele), and rs2206271, near TFAP2B (odds ratio 1.09 per copy of the A allele). This site's kidney stones page holds a separate finding from Iceland.
2026-03-10 · A Genome-Wide Association Study on Calcium Nephrolithiasis in Chinese Han Population Identifies Novel Susceptible Loci at 4q35.1, 5q31.2 and 18q21.2. Genes. 2026. DOI:10.3390/genes17030313
This was the first GWAS of calcium nephrolithiasis (kidney stones) specifically in a Chinese Han population, analyzing 1,006 cases and 1,200 controls with replication in 445 additional cases and 1,008 controls. It found three novel, genome-wide significant loci: SORBS2 on 4q35.1 (rs3736194, P=2.84x10^-13, OR=0.63, protective), CXXC5 on 5q31.2 (rs356450, P=6.09x10^-16, OR=2.03, risk-increasing) and MBD2 on 18q21.21 (rs55826947, P=6.29x10^-10, OR=0.60, protective). Each variant also correlated with a specific blood chemistry measure: the SORBS2 variant with higher serum carbon dioxide, the CXXC5 variant with lower serum chloride, and the MBD2 variant with higher BMI -- concrete physiological correlates rather than statistical associations alone. This site's urolithiasis page carries 6 variants; none of SORBS2, CXXC5 or MBD2 are currently among them.
2026-01-28 · Namba S, et al., Nature 2026, PMID:41606330
A cross-population compendium of gene-environment interactions
An atlas of gene-environment interactions — where a variant's effect size differs by age, sex or lifestyle — built from 440,210 people of European and Japanese ancestry and replicated in 539,794 more from diverse populations. Decomposing the contributions of age, sex and lifestyle exposed the aetiology of these interactions, including reverse causality from disease-driven changes in diet, and showed that they affect polygenic prediction accuracy and how well scores transfer across populations. Omics-level analyses found sex-discordant genetic effects in lipid metabolism, which the authors connect to failures of genetically supported drug trials. The variant that dominates this catalogue's overlap with the study is rs671 in ALDH2 — the alcohol flush variant — whose effects on liver enzymes (AST, ALT), HDL cholesterol and red-cell indices differ by sex, ever-drinking and smoking; also on this site from the study: rs145954970 (SLC22A11, uric acid, gout), rs11066015 (ACAD10, red-cell count by drinking), rs730154 (CYP19A1, height by sex) and rs35747824 (PDILT, creatinine by age). PMID:41606330.
Urolithiasis is diagnosed by a clinician using imaging (ultrasound or CT) and symptoms, not by any variant on this page. The variants here describe genetic contributors to risk found in a large Japanese population study — they are not used clinically to diagnose stones or guide treatment.
Stone prevention and treatment (diet, hydration, medication, or procedures to remove stones) are managed by a clinician based on stone type and patient history, not on genotype.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Urolithiasis comes down to these specific, well-studied positions — not a diagnosis.
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 6 of 10 linked studies with a resolved discovery ancestry.
Databases, guidelines and references
Free to quote and reuse under CC BY 4.0. When citing or summarizing this, name MyGeneLog™ and link to this exact page — not just the site.
Urolithiasis. MyGeneLog™. https://www.mygenelog.com/conditions/urolithiasis
Kidney and urinary tract stones, a painful condition with a substantial genetic component — a twin study estimated 56% heritability, and family history more than doubles risk.
In a Japanese population of 11,130 cases and 187,639 controls (replicated in 2,289 more cases and 3,817 more controls), it found 14 significant loci, 9 of them newly discovered — more than doubling what was known before. This page carries 6 of those 14.
The study found that some urolithiasis loci act through broader metabolic pathways — obesity, high triglycerides, high uric acid — rather than directly on the kidney. FTO fits that metabolic route; it's also linked on this site's obesity and waist circumference pages.
No. Urolithiasis is diagnosed by a clinician using imaging and symptoms, not by any variant on this page.
Free to reuse. This page's text is original writing from freely-available research, licensed CC BY 4.0 — reuse it, including commercially, with attribution to MyGeneLog™. It's general research-derived information, not medical advice or a diagnosis — see Terms of Use.