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Hum Mol Genet. 2018 Jun 1;27(11):2025-2038. doi: 10.1093/hmg/ddy121.

Genome-wide association study identifies nine novel loci for 2D:4D finger ratio, a putative retrospective biomarker of testosterone exposure in utero.

Author information

1
The University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, QLD 4102, Australia.
2
Queensland Institute of Medical Research, Brisbane, QLD 4006, Australia.
3
Division of Obstetrics and Gynaecology, The University of Western Australia, Perth, WA 6009, Australia.
4
The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, 3015 CN, Rotterdam, South Holland, The Netherlands.
5
Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, 3015 CN, Rotterdam, The Netherlands.
6
MRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK.
7
Population Health Sciences, University of Bristol, Bristol BS8 2PS, UK.
8
Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK.
9
23andMe, Inc., Mountain View, CA 94061, USA.
10
School of Medicine and Public Health, Faculty of Medicine and Health, The University of Newcastle, Newcastle, NSW 2308, Australia.
11
Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, 3015 CN, Rotterdam, Netherlands.
12
Department of Obstetrics and Gynaecology, The University of Melbourne and the Royal Women's Hospital, Parkville, VIC 3052, Australia.
13
Department of Psychology and Warwick Medical School, University of Warwick, Coventry CV47AL, UK.
14
Queensland Brain Institute and Centre for Advanced Imaging, University of Queensland, Brisbane, QLD 4072, Australia.
15
Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, 3015 CN, Rotterdam, The Netherlands.
16
Lions Eye Institute, Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, WA 6009, Australia.

Abstract

The ratio of the length of the index finger to that of the ring finger (2D:4D) is sexually dimorphic and is commonly used as a non-invasive biomarker of prenatal androgen exposure. Most association studies of 2D:4D ratio with a diverse range of sex-specific traits have typically involved small sample sizes and have been difficult to replicate, raising questions around the utility and precise meaning of the measure. In the largest genome-wide association meta-analysis of 2D:4D ratio to date (N = 15 661, with replication N = 75 821), we identified 11 loci (9 novel) explaining 3.8% of the variance in mean 2D:4D ratio. We also found weak evidence for association (β = 0.06; P = 0.02) between 2D:4D ratio and sensitivity to testosterone [length of the CAG microsatellite repeat in the androgen receptor (AR) gene] in females only. Furthermore, genetic variants associated with (adult) testosterone levels and/or sex hormone-binding globulin were not associated with 2D:4D ratio in our sample. Although we were unable to find strong evidence from our genetic study to support the hypothesis that 2D:4D ratio is a direct biomarker of prenatal exposure to androgens in healthy individuals, our findings do not explicitly exclude this possibility, and pathways involving testosterone may become apparent as the size of the discovery sample increases further. Our findings provide new insight into the underlying biology shaping 2D:4D variation in the general population.

PMID:
29659830
PMCID:
PMC5961159
DOI:
10.1093/hmg/ddy121
[Indexed for MEDLINE]
Free PMC Article

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