TY - JOUR
T1 - 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
T2 - A trans-ethnic meta-analysis
AU - Fernández-Rhodes, Lindsay
AU - Malinowski, Jennifer R.
AU - Wang, Yujie
AU - Tao, Ran
AU - Pankratz, Nathan
AU - Jeff, Janina M.
AU - Yoneyama, Sachiko
AU - Carty, Cara L.
AU - Setiawan, V. Wendy
AU - Le Marchand, Loic
AU - Haiman, Christopher
AU - Corbett, Steven
AU - Demerath, Ellen
AU - Heiss, Gerardo
AU - Gross, Myron
AU - Buzkova, Petra
AU - Crawford, Dana C.
AU - Hunt, Steven C.
AU - Rao, D. C.
AU - Schwander, Karen
AU - Chakravarti, Aravinda
AU - Gottesman, Omri
AU - Abul-Husn, Noura S.
AU - Bottinger, Erwin P.
AU - Loos, Ruth J.F.
AU - Raffel, Leslie J.
AU - Yao, Jie
AU - Guo, Xiuqing
AU - Bielinski, Suzette J.
AU - Rotter, Jerome I.
AU - Vaidya, Dhananjay
AU - Chen, Yii Der Ida
AU - Castañeda, Sheila F.
AU - Daviglus, Martha
AU - Kaplan, Robert
AU - Talavera, Gregory A.
AU - Ryckman, Kelli K.
AU - Peters, Ulrike
AU - Ambite, Jose Luis
AU - Buyske, Steven
AU - Hindorff, Lucia
AU - Kooperberg, Charles
AU - Matise, Tara
AU - Franceschini, Nora
AU - North, Kari E.
N1 - Publisher Copyright:
© Public Library of Science. All rights reserved.
PY - 2018/7
Y1 - 2018/7
N2 - 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-valuesbinomial0.01). 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.
AB - 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-valuesbinomial0.01). 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.
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U2 - 10.1371/journal.pone.0200486
DO - 10.1371/journal.pone.0200486
M3 - Article
C2 - 30044860
AN - SCOPUS:85050732362
SN - 1932-6203
VL - 13
JO - PloS one
JF - PloS one
IS - 7
M1 - e0200486
ER -