A genome-wide scan for naevus count: linkage to CDKN2A and to other chromosome regions

Abstract

High numbers of melanocytic naevi (moles), and mutations in the p16 gene (CDKN2A), are two strong risk factors for cutaneous malignant melanoma. We have previously reported linkage of mole count to the CDKN2A locus. Here, we report genome-wide scans for mole counts (differentiated into flat, raised and atypical subtypes) with a total of 796 microsatellite markers for 424 families with 1024 twins and siblings, plus genotypes for 690 parents. Inclusion of 221 pairs of MZ twins enabled separation of shared environmental and polygenic influences, so placing an upper limit to estimates of QTL variance. Maximum likelihood multipoint variance component methods were used to assess linkage of naevus count. Sex, age, body surface area, skin colour, hair colour, sunburn and facial freckles were included as covariates. Peak linkage of flat mole count was to regions on chromosomes 2, 9, 8 and 17 with lod scores 2.95, 2.95, 2.50 and 2.15, respectively. The support for linkage to the CDKN2A gene region (9p21) increased to 3.42 when additional fine mapping markers were added. For raised mole count, there was suggestive evidence of linkage in our sample to chromosome 16 (lod ¼ 1.87), and for atypical mole count on chromosomes 1, 6 and X with lod scores of 2.20, 2.00 and 2.00, respectively. The multivariate linkage peaks generally match those from individual trait analyses, with the exception of a new peak on chromosome 4 (point-wise empirical P-value ¼ 0.001). We replicate our earlier finding of linkage to CDKN2A and discovering linkage to several novel regions that may also influence risk of the development of malignant melanoma.

Genome-wide linkage scan for atypical nevi in p16-Leiden melanoma families

“…Only recently, two papers have been published on genome-wide scans for nevi: Falchi et al 25 have undertaken an analysis of total nevus count in 194 twin families and Zhu et al 26 report genome-wide scans for flat, raised and atypical nevi in 424 twin families. Although each of these studies have used different phenotype definitions, it is difficult to overlook a shared increased LOD score on chromosome 9q; we report an LOD score of 1.49 for marker D9S283 on 9q22, for which Zhu et al 26 report an LOD score of 1.78. Falchi et al 25 report an LOD score of 2.55 on marker D9S167, which is more proximal on 9q21.…”

Family-based mitochondrial association study of traits related to type 2 diabetes and the metabolic syndrome in adolescents

“…Table 2 gives the breakdown of the number of individuals measured at each time point and the overlap between the groups. The sample has been shown to be representative of the general Queensland population with respect to cognition [29] and skin mole counts [31]. Further information on the sample, including recruitment strategy, have been described previously [31,32].…”

The Heritability and Genetic Correlates of Mobile Phone Use: A Twin Study of Consumer Behavior

“…Teenaged twins were recruited from schools in Brisbane, Australia, and surrounding areas, in the context of studies on melanoma risk factors (see Zhu et al, 2007, for details) and on biological markers of cognitive abilities (see Wright and Martin, 2004 for details). Sample 1 (the melanoma risk study) included 548 participants from 274 families, including 88 MZ and 185 DZ twin pairs, mostly aged 14 years.…”