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. |
Publication Type | Publication |
Year | 2018 |
Authors | Fernández-Rhodes L, Malinowski JR, Wang Y, Tao R, Pankratz N, Jeff JM, Yoneyama S, Carty CL, V Setiawan W, Le Marchand L, Haiman C, Corbett S, Demerath E, Heiss G, Gross M, Buzkova P, Crawford DC, Hunt SC, Rao DC, Schwander K, Chakravarti A, Gottesman O, Abul-Husn NS, Bottinger EP, Loos RJF, Raffel LJ, Yao J, Guo X, Bielinski SJ, Rotter JI, Vaidya D, Chen Y-DIda, Castañeda SF, Daviglus M, Kaplan R, Talavera GA, Ryckman KK, Peters U, Ambite JLuis, Buyske S, Hindorff L, Kooperberg C, Matise T, Franceschini N, North KE |
Journal | PLoS One |
Volume | 13 |
Issue | 7 |
Pagination | e0200486 |
Date Published | 2018 |
ISSN | 1932-6203 |
Keywords | Age Factors, Alleles, Biological Variation, Population, Female, Genetic Loci, Genotype, Humans, Menarche, Menopause, Phenotype, Polymorphism, Single Nucleotide |
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. |
DOI | 10.1371/journal.pone.0200486 |
Alternate Journal | PLoS One |
PubMed ID | 30044860 |
PubMed Central ID | PMC6059436 |
Grant List | U01 HG007419 / HG / NHGRI NIH HHS / United States R01 HL071251 / HL / NHLBI NIH HHS / United States R01 HL071259 / HL / NHLBI NIH HHS / United States UL1 TR001420 / TR / NCATS NIH HHS / United States R01 HL071258 / HL / NHLBI NIH HHS / United States UL1 TR000040 / TR / NCATS NIH HHS / United States HHSN268201100008C / HL / NHLBI NIH HHS / United States U01 HG007417 / HG / NHGRI NIH HHS / United States U01 HG004798 / HG / NHGRI NIH HHS / United States R01 HD057194 / HD / NICHD NIH HHS / United States U01 HG004802 / HG / NHGRI NIH HHS / United States R01 HL086694 / HL / NHLBI NIH HHS / United States HHSN263201500003I / NH / NIH HHS / United States U01 HG004801 / HG / NHGRI NIH HHS / United States HHSN268201300028C / HL / NHLBI NIH HHS / United States UL1 TR001881 / TR / NCATS NIH HHS / United States HHSN268201300027C / HL / NHLBI NIH HHS / United States HHSN268201100007C / HL / NHLBI NIH HHS / United States U01 HG007416 / HG / NHGRI NIH HHS / United States HHSN268200900041C / HL / NHLBI NIH HHS / United States HHSN268201100011C / HL / NHLBI NIH HHS / United States R01 DK089256 / DK / NIDDK NIH HHS / United States U01 HG007376 / HG / NHGRI NIH HHS / United States / RA / ARRA NIH HHS / United States R01 HL071051 / HL / NHLBI NIH HHS / United States R01 HL071205 / HL / NHLBI NIH HHS / United States UL1 RR025005 / RR / NCRR NIH HHS / United States U01 HG004402 / HG / NHGRI NIH HHS / United States HHSN268201300029C / HL / NHLBI NIH HHS / United States HHSN268201300025C / HL / NHLBI NIH HHS / United States R56 HG010297 / HG / NHGRI NIH HHS / United States U01 CA136792 / CA / NCI NIH HHS / United States HHSN268201100012C / HL / NHLBI NIH HHS / United States UL1 RR033176 / RR / NCRR NIH HHS / United States HHSN268201100005C / HL / NHLBI NIH HHS / United States R01 HL087641 / HL / NHLBI NIH HHS / United States HHSN268201100009C / HL / NHLBI NIH HHS / United States UL1 TR001079 / TR / NCATS NIH HHS / United States S10 OD020069 / OD / NIH HHS / United States HHSN268201100006C / HL / NHLBI NIH HHS / United States R01 DK101855 / DK / NIDDK NIH HHS / United States P2C HD050924 / HD / NICHD NIH HHS / United States T32 HL007055 / HL / NHLBI NIH HHS / United States R01 HL071250 / HL / NHLBI NIH HHS / United States P30 CA071789 / CA / NCI NIH HHS / United States HHSN268201300026C / HL / NHLBI NIH HHS / United States U01 HG004790 / HG / NHGRI NIH HHS / United States U01 HG004803 / HG / NHGRI NIH HHS / United States HHSN268201100010C / HL / NHLBI NIH HHS / United States P50 ES015915 / ES / NIEHS NIH HHS / United States R01 CA063464 / CA / NCI NIH HHS / United States UL1 TR000445 / TR / NCATS NIH HHS / United States |
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.
MS#:
0281
ECI:
Yes
Manuscript Status:
Published