Genome-wide linkage analysis to age at natural menopause in a community-based sample: the Framingham Heart Study

Objective: To identify chromosomal regions linked to age at natural menopause. Design: Two-generation families studied with a 10-centimorgan (cM) genome-wide scan. Setting: The Framingham Study, a community-based epidemiologic study: Patient(s): A total of 861 women in 291 families reporting a natural menopause (mean age at menopause, 49 years). Intervention(s): None: Main Outcome Measure(s): Multipoint variance components linkage analysis was performed with Genehunter software (Whitehead Institute, Massachusetts Institute of Technology, Boston, MA) forage at natural menopause. Result(s): In the crude variance components analysis, 11 chromosomes had a log odds ratio (LOD) score of >= 1.0. Two chromosomal regions revealed suggestive linkage: chromosome 8 at 26 cM (LOD 2.6; nearest marker GATA23D06) and chromosome 16 at 11 cM (LOD 2.4; nearest marker ATA41E04). In the analysis adjusted for generation, smoking, and body mass index, chromosome 11 revealed suggestive linkage at 113 cM (LOD 2.1; nearest marker GATA23E06). Conclusion(s): We have identified novel loci suggestive for linkage to age at natural menopause. Further research is needed to identify genes involved in the onset of menopause, which might provide insights into loss of fertility.