A genome wide linkage scan for dizygotic twinning in 525 families of mothers of dizygotic twins

Painter, J. N., Willemsen, G., Nyholt, D.R., Hoekstra, C., Duffy, D. L., Henders, A. K., Wallace, L., Healey, S., Cannon-Albright, L. A., Skolnick, M., Martin, N. G., Boomsma, D. I., & Montgomery, G. W. (2010) A genome wide linkage scan for dizygotic twinning in 525 families of mothers of dizygotic twins. Human Reproduction, 25(2), pp. 1569-1580.

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The tendency to conceive dizygotic (DZ) twins is a complex trait influenced by genetic and environmental factors. To search for new candidate loci for twinning, we conducted a genome-wide linkage scan in 525 families using microsatellite and single nucleotide polymorphism marker panels.


Non-parametric linkage analyses, including 523 families containing a total of 1115 mothers of DZ twins (MODZT) from Australia and New Zealand (ANZ) and The Netherlands (NL), produced four linkage peaks above the threshold for suggestive linkage, including a highly suggestive peak at the extreme telomeric end of chromosome 6 with an exponential logarithm of odds [(exp)LOD] score of 2.813 (P = 0.0002). Since the DZ twinning rate increases steeply with maternal age independent of genetic effects, we also investigated linkage including only families where at least one MODZT gave birth to her first set of twins before the age of 30. These analyses produced a maximum expLOD score of 2.718 (P = 0.0002), largely due to linkage signal from the ANZ cohort, however, ordered subset analyses indicated this result is most likely a chance finding in the combined dataset. Linkage analyses were also performed for two large DZ twinning families from the USA, one of which produced a peak on chromosome 2 in the region of two potential candidate genes. Sequencing of FSHR and FIGLA, along with INHBB in MODZTs from two large NL families with family specific linkage peaks directly over this gene, revealed a potentially functional variant in the 5' untranslated region of FSHR that segregated with the DZ twinning phenotype in the Utah family.


Our data provide further evidence for complex inheritance of familial DZ twinning.

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ID Code: 91975
Item Type: Journal Article
Refereed: Yes
Additional Information: Painter, Jodie N Willemsen, Gonneke Nyholt, Dale Hoekstra, Chantal Duffy, David L Henders, Anjali K Wallace, Leanne Healey, Sue Cannon-Albright, Lisa A Skolnick, Mark Martin, Nicholas G Boomsma, Dorret I Montgomery, Grant W eng HD042157/HD/NICHD NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England Oxford, England 2010/04/10 06:00 Hum Reprod. 2010 Jun;25(6):1569-80. doi: 10.1093/humrep/deq084. Epub 2010 Apr 8.
Keywords: Australia, Family, Female, Genetic Linkage/*genetics, Genome-Wide Association Study, Genotype, Humans, Male, Maternal Age, Netherlands, New Zealand, Phenotype, Twins, Dizygotic/*genetics
DOI: 10.1093/humrep/deq084
ISSN: 0268-1161
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2010 The Author
Deposited On: 18 Jan 2016 01:21
Last Modified: 15 Feb 2016 22:02

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