Genome-wide scan and fine-mapping linkage study of androgenetic alopecia reveals a locus on chromosome 3q26

Abstract

Androgenetic alopecia (AGA, male pattern baldness) is the most common form of hair loss. The origin of AGA is genetic, with the X chromosome located androgen receptor gene (AR) being the only risk gene identified to date. We present the results of a genome-wide linkage study of 95 families and linkage fine mapping of the 3q21-q29, 11q14-q25, 18p11-q23, and 19p13-q13 regions in an extended sample of 125 families of German descent. The locus with strongest evidence for linkage was mapped to 3q26 with a nonparametric linkage (NPL) score of 3.97 (empirical p value = 0.00055). This is the first step toward the identification of new susceptibility genes in AGA, a process which will provide important insights into the molecular and cellular basis of scalp hair loss.

Figure 1

Genome-wide Linkage Analysis of 95 Families with Early-Onset AGA The multipoint NPL score is shown on the vertical axis, and the distance (in cM, Duffy's integrated map) is given on the horizontal axis.

Figure 2

MOD-Score Analysis of Four Chromosomes Analysis of chromosomes 3, 11, 18, and 19 was performed in 95 families with early-onset AGA. The multipoint LOD and NPL scores are shown on the vertical axis, and the distance (in cM, Duffy's integrated map) is given on the horizontal axis. Dotted lines indicate LOD scores, and solid lines indicate NPL scores.

Figure 3

Fine-Mapping Linkage Analysis of Four Chromosomal Regions The multipoint NPL score is shown on the vertical axis and the distance (top; in cM, Duffy's integrated map) and positions of the fine-mapping STR markers (bottom) on the horizontal axis. Dashed lines indicate NPL scores of the genome scan, thin lines indicate NPL scores of the fine-mapping marker set in families of the genome scan, and thick lines indicate NPL scores of the fine-mapping marker set in extended-family sample.

Figure 4

Interaction Scan for AGA between the AR Locus and the Autosomes Boxes indicate the interaction between eight STR marker (DXS7132–DXS6800) spanning 8 cM around the AR gene on the horizontal axis in cM (Duffy's map) and the autosomal chromosomes, as indicated on the vertical axis in cM (Duffy's map). Fine-mapping linkage regions with NPL scores greater than 1 are indicated by red vertical bars. The various levels of ΔNPL scores are presented with different colors: Red indicates ΔNPL scores of at least 3, yellow indicates ΔNPL scores of 2, green indicates ΔNPL scores of 1, blue indicates ΔNPL scores of no more than 0.