A variant in LIN28B is associated with 2D:4D finger-length ratio, a putative retrospective biomarker of prenatal testosterone exposure

Abstract

The ratio of the lengths of an individual's second to fourth digit (2D:4D) is commonly used as a noninvasive retrospective biomarker for prenatal androgen exposure. In order to identify the genetic determinants of 2D:4D, we applied a genome-wide association approach to 1507 11-year-old children from the Avon Longitudinal Study of Parents and Children (ALSPAC) in whom 2D:4D ratio had been measured, as well as a sample of 1382 12- to 16-year-olds from the Brisbane Adolescent Twin Study. A meta-analysis of the two scans identified a single variant in the LIN28B gene that was strongly associated with 2D:4D (rs314277: p = 4.1 x 10(-8)) and was subsequently independently replicated in an additional 3659 children from the ALSPAC cohort (p = 1.53 x 10(-6)). The minor allele of the rs314277 variant has previously been linked to increased height and delayed age at menarche, but in our study it was associated with increased 2D:4D in the direction opposite to that of previous reports on the correlation between 2D:4D and age at menarche. Our findings call into question the validity of 2D:4D as a simplistic retrospective biomarker for prenatal testosterone exposure.

Figure 1

Plot of the Locus Surrounding LIN28B SNPs are plotted by position on chromosome 6 (build 36) against GWAS p values for average 2D:4D. SNP rs314277 is shown in dark red labeled with its p value in the discovery meta-analysis. Estimated recombination rates from HapMap are plotted in light blue to reflect local LD structure. The directly genotyped or imputed SNPs surrounding rs314277 are color coded to reflect their LD with rs314277 (according to pair-wise r² values from the HapMap CEU database). Genes and their direction of transcription are labeled at the bottom of the plot.