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.SNPedia illustrates population differences at rs314277. Asians (CHB, CHD, JPT) show very low frequencies of the minor allele; blacks (YRI, ASW, LWK, MKK) show relatively high frequencies; and Europeans (CEU, TSI) are intermediate. This is actually the reverse of the pattern we might have expected, but many other genetic variants undoubtedly influence traits such as digit ratio and age at menarche and the fundamental issue remains.
[Medland et al. A variant in LIN28B is associated with 2D:4D finger-length ratio, a putative retrospective biomarker of prenatal testosterone exposure. Am J Hum Genet. 2010 Apr 9;86(4):519-25. Epub 2010 Mar 18.]
A genetic variant influencing digit ratio
Some recently-published research reinforces my doubts about the meaningfulness of attempts to infer cross-racial differences in prenatal androgen exposure from cross-racial differences in digit ratio: