rs10783478 (FIGNL2): Energy Intake and Expenditure

Key takeaways

• Genetic signals near ANKRD33 on chromosome 12q13 were genome-wide significantly associated with higher total energy intake specifically in men, in a study of roughly 18,700 European-ancestry adults
• Signals in the 2q22 region were linked to energy expenditure only among lean individuals in the same genome-wide study
• This variant reduces FIGNL2 (Fidgetin-like 2) expression in subcutaneous fat tissue and ANKRD33 expression in brain cortex and tibial nerve, based on large-scale gene-expression data
• Common genetic variants explain an estimated 6% of energy intake variation, but the genetic contribution to energy expenditure was not statistically detectable in this study
• All findings are preliminary, with energy intake measured by food frequency questionnaire and no independent replication cohort described

What the research says A pooled genome-wide association study (GWAS - a scan of hundreds of thousands of genetic variants across the genome at once) of 12,030 European-ancestry women and 6,743 men estimated that common genetic variants explain about 6% of the variation in total energy intake (heritability 6.05%, 95% CI 1.76-10.34, P = 0.006), while no statistically significant heritable fraction was detected for energy expenditure. Three variants on chromosome 12q13 near ANKRD33 (ankyrin repeat domain 33) reached genome-wide significance for higher total energy intake in men, and separate signals in the 2q22 region were associated with energy expenditure in lean individuals; BMI-related variants were also found to overlap significantly with energy trait signals. Gene-expression data from GTEx v11 (953 donors, cis-window, FDR < 0.05) links this specific variant to reduced FIGNL2 expression in subcutaneous fat and reduced ANKRD33 expression in brain cortex and tibial nerve GTEx Portal.

Reported associations

• Total energy intake (men only): Genome-wide significant signals near ANKRD33 on chromosome 12q13 were associated with increased total energy intake in European-ancestry men in a pooled GWAS of approximately 18,700 participants
• Energy expenditure (lean individuals): Signals in the 2q22 region were associated with energy expenditure specifically among lean people in the same GWAS
• FIGNL2 gene expression - subcutaneous fat: This variant is associated with reduced FIGNL2 expression in subcutaneous adipose (under-skin fat) tissue GTEx Portal
• ANKRD33 gene expression - brain and nerve: This variant is associated with reduced ANKRD33 expression in brain cortex and tibial nerve (a major nerve running through the lower leg) GTEx Portal

Evidence quality The energy-trait associations come from a single pooled GWAS of 18,773 European-ancestry participants drawn from the Nurses' Health Studies and the Health Professionals Follow-up Study. Energy intake was measured by food frequency questionnaire (FFQ), which the study authors acknowledge carries substantial measurement error relative to gold-standard methods such as doubly labeled water or seven-day food records. No independent replication cohort is described in the available text, and the study authors explicitly call for larger GWAS to confirm findings. The SNP heritability estimate for energy intake was statistically significant (P = 0.006) but carried a wide confidence interval (1.76-10.34%), reflecting limited precision. The heritability of energy expenditure was not significantly different from zero, suggesting limited statistical power for that trait. The GTEx eQTL signals passed a false discovery rate (FDR) threshold below 0.05 across 953 donors: the ANKRD33 association reached p = 1.0e-5 in brain cortex and p = 8.2e-11 in tibial nerve; the FIGNL2 adipose association reached p = 6.7e-6. These expression effects are mechanistic (they show how gene activity differs by genotype) and do not on their own establish disease risk or clinical relevance.

Tissue-specific expression effects

• FIGNL2: The ALT allele at this variant is associated with reduced FIGNL2 expression in subcutaneous adipose tissue GTEx Portal
• ANKRD33: The same allele is associated with reduced ANKRD33 expression in brain cortex and tibial nerve tissue GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.