David A Hinds

Publications (2)15.01 Total impact

• Article: Androgenetic alopecia: identification of four genetic risk loci and evidence for the contribution of WNT-signaling to its etiology.

  Stefanie Heilmann, Amy K Kiefer, Nadine Fricker, Dmitriy Drichel, Axel M Hillmer, Christine Herold, Joyce Y Tung, Nicholas Eriksson, Silke Redler, Regina C Betz, [......], George Dedoussis, Nicholas G Martin, Lambertus A Kiemeney, Vincent Mooser, Kari Stefansson, J Brent Richards, Tim Becker, Felix F Brockschmidt, David A Hinds, Markus M Nöthen
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  ABSTRACT: The pathogenesis of androgenetic alopecia (AGA, male-pattern baldness) is driven by androgens, and genetic predisposition is the major prerequisite. Candidate gene and genome-wide association studies have reported that single nucleotide polymorphisms (SNPs) at eight different genomic loci are associated with AGA-development. However a significant fraction of the overall heritable risk still awaits identification. Furthermore, understanding of the pathophysiology of AGA is incomplete, and each newly associated locus may provide novel insights into contributing biological pathways. The aim of this study was to identify unknown AGA risk loci by replicating SNPs at the twelve genomic loci that showed suggestive association (5 × 10(-8)<P<10(-5)) with AGA in a recent meta-analysis. We analyzed a replication-set comprising 2,759 cases and 2,661 controls of European descent to confirm the association with AGA at these loci. Combined analysis of the replication and the meta-analysis data identified four genome-wide significant risk loci for AGA on chromosomes 2q35, 3q25.1, 5q33.3, and 12p12.1. The strongest association signal was obtained for rs7349332 (P=3.55 × 10(-15)) on chr2q35, which is located intronically in WNT10A. Expression studies in human hair follicle tissue suggest that WNT10A plays a functional role in AGA-etiology. Thus, our study provides genetic evidence supporting an involvement of WNT-signaling in AGA-development.Journal of Investigative Dermatology accepted article preview online, 28 January 2013;. doi:10.1038/jid.2013.43.
  Journal of Investigative Dermatology 01/2013; · 6.31 Impact Factor
• Source

  Available from: Felix F Brockschmidt

  Article: Six novel susceptibility Loci for early-onset androgenetic alopecia and their unexpected association with common diseases.

  Rui Li, Felix F Brockschmidt, Amy K Kiefer, Hreinn Stefansson, Dale R Nyholt, Kijoung Song, Sita H Vermeulen, Stavroula Kanoni, Daniel Glass, Sarah E Medland, [......], Peter Vollenweider, Tim D Spector, George Dedoussis, Nicholas G Martin, Lambertus A Kiemeney, Vincent Mooser, Kari Stefansson, David A Hinds, Markus M Nöthen, J Brent Richards
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  ABSTRACT: Androgenetic alopecia (AGA) is a highly heritable condition and the most common form of hair loss in humans. Susceptibility loci have been described on the X chromosome and chromosome 20, but these loci explain a minority of its heritable variance. We conducted a large-scale meta-analysis of seven genome-wide association studies for early-onset AGA in 12,806 individuals of European ancestry. While replicating the two AGA loci on the X chromosome and chromosome 20, six novel susceptibility loci reached genome-wide significance (p = 2.62×10⁻⁹-1.01×10⁻¹²). Unexpectedly, we identified a risk allele at 17q21.31 that was recently associated with Parkinson's disease (PD) at a genome-wide significant level. We then tested the association between early-onset AGA and the risk of PD in a cross-sectional analysis of 568 PD cases and 7,664 controls. Early-onset AGA cases had significantly increased odds of subsequent PD (OR = 1.28, 95% confidence interval: 1.06-1.55, p = 8.9×10⁻³). Further, the AGA susceptibility alleles at the 17q21.31 locus are on the H1 haplotype, which is under negative selection in Europeans and has been linked to decreased fertility. Combining the risk alleles of six novel and two established susceptibility loci, we created a genotype risk score and tested its association with AGA in an additional sample. Individuals in the highest risk quartile of a genotype score had an approximately six-fold increased risk of early-onset AGA [odds ratio (OR) = 5.78, p = 1.4×10⁻⁸⁸]. Our results highlight unexpected associations between early-onset AGA, Parkinson's disease, and decreased fertility, providing important insights into the pathophysiology of these conditions.
  PLoS Genetics 05/2012; 8(5):e1002746. · 8.69 Impact Factor