The genetic underpinnings of variation in ages at menarche and natural menopause among women from the multi-ethnic Population Architecture using Genomics and Epidemiology (PAGE) Study: A trans-ethnic meta-analysis.

The genetic underpinnings of variation in ages at menarche and natural menopause among women from the multi-ethnic Population Architecture using Genomics and Epidemiology (PAGE) Study: A trans-ethnic meta-analysis. Fernández-Rhodes, L., Malinowski, J. R., Wang, Y., Tao, R., Pankratz, N., Jeff, J. M., Yoneyama, S., Carty, C. L., Setiawan, V. W., Le Marchand, L., Haiman, C., Corbett, S., Demerath, E., Heiss, G., Gross, M., Buzkova, P., Crawford, D. C., Hunt, S. C., Rao, D. C., Schwander, K., Chakravarti, A., Gottesman, O., Abul-Husn, N. S., Bottinger, E. P., Loos, R. J. F., Raffel, L. J., Yao, J., Guo, X., Bielinski, S. J., Rotter, J. I., Vaidya, D., Chen, Y. I., Castañeda, S. F., Daviglus, M., Kaplan, R., Talavera, G. A., Ryckman, K. K., Peters, U., Ambite, J. L., Buyske, S., Hindorff, L., Kooperberg, C., Matise, T., Franceschini, N., & North, K. E. PloS one, 13:e0200486, 2018.

Paper doi abstract bibtex

Current knowledge of the genetic architecture of key reproductive events across the female life course is largely based on association studies of European descent women. The relevance of known loci for age at menarche (AAM) and age at natural menopause (ANM) in diverse populations remains unclear. We investigated 32 AAM and 14 ANM previously-identified loci and sought to identify novel loci in a trans-ethnic array-wide study of 196,483 SNPs on the MetaboChip (Illumina, Inc.). A total of 45,364 women of diverse ancestries (African, Hispanic/Latina, Asian American and American Indian/Alaskan Native) in the Population Architecture using Genomics and Epidemiology (PAGE) Study were included in cross-sectional analyses of AAM and ANM. Within each study we conducted a linear regression of SNP associations with self-reported or medical record-derived AAM or ANM (in years), adjusting for birth year, population stratification, and center/region, as appropriate, and meta-analyzed results across studies using multiple meta-analytic techniques. For both AAM and ANM, we observed more directionally consistent associations with the previously reported risk alleles than expected by chance (p-valuesbinomial≤0.01). Eight densely genotyped reproductive loci generalized significantly to at least one non-European population. We identified one trans-ethnic array-wide SNP association with AAM and two significant associations with ANM, which have not been described previously. Additionally, we observed evidence of independent secondary signals at three of six AAM trans-ethnic loci. Our findings support the transferability of reproductive trait loci discovered in European women to women of other race/ethnicities and indicate the presence of additional trans-ethnic associations both at both novel and established loci. These findings suggest the benefit of including diverse populations in future studies of the genetic architecture of female growth and development.

@article{FernandezRhodesMalinowskiWangEtAl2018,
	abstract = {Current knowledge of the genetic architecture of key reproductive events across the female life course is largely based on association studies of European descent women. The relevance of known loci for age at menarche (AAM) and age at natural menopause (ANM) in diverse populations remains unclear. We investigated 32 AAM and 14 ANM previously-identified loci and sought to identify novel loci in a trans-ethnic array-wide study of 196,483 SNPs on the MetaboChip (Illumina, Inc.). A total of 45,364 women of diverse ancestries (African, Hispanic/Latina, Asian American and American Indian/Alaskan Native) in the {Population Architecture using Genomics and Epidemiology} (PAGE) Study were included in cross-sectional analyses of AAM and ANM. Within each study we conducted a linear regression of {SNP} associations with self-reported or medical record-derived AAM or ANM (in years), adjusting for birth year, population stratification, and center/region, as appropriate, and meta-analyzed results across studies using multiple meta-analytic techniques. For both AAM and ANM, we observed more directionally consistent associations with the previously reported risk alleles than expected by chance (p-valuesbinomial≤0.01). Eight densely genotyped reproductive loci generalized significantly to at least one non-European population. We identified one trans-ethnic array-wide {SNP} association with AAM and two significant associations with ANM, which have not been described previously. Additionally, we observed evidence of independent secondary signals at three of six AAM trans-ethnic loci. Our findings support the transferability of reproductive trait loci discovered in European women to women of other race/ethnicities and indicate the presence of additional trans-ethnic associations both at both novel and established loci. These findings suggest the benefit of including diverse populations in future studies of the genetic architecture of female growth and development.},
	author = {Fern{\'a}ndez-Rhodes, Lindsay and Malinowski, Jennifer R. and Wang, Yujie and Tao, Ran and Pankratz, Nathan and Jeff, Janina M. and Yoneyama, Sachiko and Carty, Cara L. and Setiawan, V. Wendy and Le Marchand, Loic and Haiman, Christopher and Corbett, Steven and Demerath, Ellen and Heiss, Gerardo and Gross, Myron and Buzkova, Petra and Crawford, Dana C. and Hunt, Steven C. and Rao, D. C. and Schwander, Karen and Chakravarti, Aravinda and Gottesman, Omri and Abul-Husn, Noura S. and Bottinger, Erwin P. and Loos, Ruth J. F. and Raffel, Leslie J. and Yao, Jie and Guo, Xiuqing and Bielinski, Suzette J. and Rotter, Jerome I. and Vaidya, Dhananjay and Chen, Yii-Der Ida and Casta{\~n}eda, Sheila F. and Daviglus, Martha and Kaplan, Robert and Talavera, Gregory A. and Ryckman, Kelli K. and Peters, Ulrike and Ambite, Jose Luis and Buyske, Steven and Hindorff, Lucia and Kooperberg, Charles and Matise, Tara and Franceschini, Nora and North, Kari E.},
	citation-subset = {IM},
	completed = {2019-01-11},
	country = {United States},
	doi = {10.1371/journal.pone.0200486},
	issn = {1932-6203},
	issn-linking = {1932-6203},
	issue = {7},
	journal = {PloS one},
	keywords = {Age Factors; Alleles; Biological Variation, Population, ethnology, genetics; Female; Genetic Loci, genetics; Genotype; Humans; Menarche, ethnology, genetics; Menopause, ethnology, genetics; Phenotype; Polymorphism, Single Nucleotide},
	nlm-id = {101285081},
	owner = {NLM},
	pages = {e0200486},
	pii = {PONE-D-18-02039},
	pmc = {PMC6059436},
	pmid = {30044860},
	url = {https://pubmed.ncbi.nlm.nih.gov/30044860/},
	pubmodel = {Electronic-eCollection},
	pubstate = {epublish},
	revised = {2020-03-09},
	title = {The genetic underpinnings of variation in ages at menarche and natural menopause among women from the multi-ethnic {Population Architecture using Genomics and Epidemiology} ({PAGE}) Study: A trans-ethnic meta-analysis.},
	volume = {13},
	year = {2018},
	bdsk-url-1 = {https://pubmed.ncbi.nlm.nih.gov/30044860/},
	bdsk-url-2 = {https://doi.org/10.1371/journal.pone.0200486}}

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