TCF7L2 polymorphisms are associated with amygdalar volume in elderly individuals with Type 2 Diabetes

Ithamar Ganmore*, Abigail Livny, Ramit Ravona-Springer, Itzik Cooper, Anna Alkelai, Shahar Shelly, Galia Tsarfaty, Anthony Heymann, Michal Schnaider Beeri, Lior Greenbaum

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The association between several Single Nucleotide Polymorphisms (SNPs) within the transcription factor 7-like 2 (TCF7L2) gene and Type 2 Diabetes (T2D) as well as additional T2D-related traits is well established. Since alteration in total and regional brain volumes are consistent findings among T2D individuals, we studied the association of four T2D susceptibility SNPS within TCF7L2 (rs7901695, rs7903146, rs11196205, and rs12255372) with volumes of white matter hyperintensities (WMH), gray matter, and regional volumes of amygdala and hippocampus obtained from structural MRI among 191 T2D elderly Jewish individuals. Under recessive genetic model (controlling for age, sex and intracranial volume), we found that for all four SNPs, carriers of two copies of the T2D risk allele (homozygous genotype) had significantly smaller amygdalar volume: rs7901695- CC genotype vs. CT + TT genotypes, p = 0.002; rs7903146-TT vs. TC + CC, p = 0.003; rs11196205- CC vs. CG + GG, p = 0.0003; and rs12255372- TT vs. TG + GG, p = 0.003. Adjusting also for T2D-related covariates, body mass index (BMI), and ancestry did not change the results substantively (rs7901695, p = 0.003; rs7903146, p = 0.005; rs11196205, p = 0.001; and rs12255372, p = 0.005). Conditional analysis demonstrated that only rs11196205 was independently associated with amygdalar volume at a significant level. Separate analysis of left and right amygdala revealed stronger results for left amygdalar volume. Taken together, we report association of TCF7L2 SNPs with amygdalar volume among T2D elderly Jewish patients. Further studies in other populations are required to support these findings and reach more definitive conclusions.

Original languageEnglish
Article number15818
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - 1 Dec 2019

Funding

FundersFunder number
LeRoy Schecter Foundation
National Institute on AgingR01 AG034087, R21 AG043878, P50AG005138
American Federation for Aging Research

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