Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
22693459
TITLE
Six novel susceptibility Loci for early-onset androgenetic alopecia and their unexpected association with common diseases.
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.
DATE PUBLISHED
2012 May
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2011/12/06
accepted 2012/04/16
epublish 2012/05/31
entrez 2012/06/14 06:00
pubmed 2012/06/14 06:00
medline 2012/09/26 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Li R Li Rui R Departments of Medicine, Human Genetics, Epidemiology, and Biostatistics, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
Brockschmidt FF Brockschmidt Felix F FF
Kiefer AK Kiefer Amy K AK
Stefansson H Stefansson Hreinn H
Nyholt DR Nyholt Dale R DR
Song K Song Kijoung K
Vermeulen SH Vermeulen Sita H SH
Kanoni S Kanoni Stavroula S
Glass D Glass Daniel D
Medland SE Medland Sarah E SE
Dimitriou M Dimitriou Maria M
Waterworth D Waterworth Dawn D
Tung JY Tung Joyce Y JY
Geller F Geller Frank F
Heilmann S Heilmann Stefanie S
Hillmer AM Hillmer Axel M AM
Bataille V Bataille Veronique V
Eigelshoven S Eigelshoven Sibylle S
Hanneken S Hanneken Sandra S
Moebus S Moebus Susanne S
Herold C Herold Christine C
den Heijer M den Heijer Martin M
Montgomery GW Montgomery Grant W GW
Deloukas P Deloukas Panos P
Eriksson N Eriksson Nicholas N
Heath AC Heath Andrew C AC
Becker T Becker Tim T
Sulem P Sulem Patrick P
Mangino M Mangino Massimo M
Vollenweider P Vollenweider Peter P
Spector TD Spector Tim D TD
Dedoussis G Dedoussis George G
Martin NG Martin Nicholas G NG
Kiemeney LA Kiemeney Lambertus A LA
Mooser V Mooser Vincent V
Stefansson K Stefansson Kari K
Hinds DA Hinds David A DA
Nöthen MM Nöthen Markus M MM
Richards JB Richards J Brent JB
INVESTIGATORS
JOURNAL
VOLUME: 8
ISSUE: 5
TITLE: PLoS genetics
ISOABBREVIATION: PLoS Genet.
YEAR: 2012
MONTH: May
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1553-7404
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: PLoS Genet
COUNTRY: United States
ISSNLINKING: 1553-7390
NLMUNIQUEID: 101239074
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
AA07535 NIAAA NIH HHS United States
AA10248 NIAAA NIH HHS United States
AA13320 NIAAA NIH HHS United States
AA13321 NIAAA NIH HHS United States
AA13326 NIAAA NIH HHS United States
AA14041 NIAAA NIH HHS United States
K05 AA017688 NIAAA NIH HHS United States
MH66206 NIMH NIH HHS United States
Canadian Institutes of Health Research Canada
Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Aged
Alleles
Alopecia genetics
Fertility genetics
Genetic Predisposition to Disease genetics
Genome-Wide Association Study genetics
Genotype genetics
Haplotypes genetics
Humans genetics
Male genetics
Middle Aged genetics
Parkinson Disease genetics
Polymorphism, Single Nucleotide genetics
Risk Factors genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC3364959 NLM