Genome-wide analysis identifies 12 loci influencing human reproductive behavior

Nicola Barban; Rick Jansen; Ronald de Vlaming; Ahmad Vaez; Jornt J Mandemakers; Felix C Tropf; Xia Shen; James F Wilson; Daniel I Chasman; Ilja M Nolte; Vinicius Tragante; Sander W van der Laan; John R B Perry; Augustine Kong; Tarunveer S Ahluwalia; Eva Albrecht; Laura Yerges-Armstrong; Gil Atzmon; Kirsi Auro; Kristin Ayers; Andrew Bakshi; Danny Ben-Avraham; Klaus Berger; Aviv Bergman; Lars Bertram; Lawrence F Bielak; Gyda Bjornsdottir; Marc Jan Bonder; Linda Broer; Minh Bui; Caterina Barbieri; Alana Cavadino; Jorge E Chavarro; Constance Turman; Maria Pina Concas; Heather J Cordell; Gail Davies; Peter Eibich; Nicholas Eriksson; Tõnu Esko; Joel Eriksson; Fahimeh Falahi; Janine F Felix; Mark Alan Fontana; Lude Franke; Ilaria Gandin; Audrey J Gaskins; Christian Gieger; Genevieve Lachance; Tim D Spector; BIOS Consortium

doi:10.1038/ng.3698

Genome-wide analysis identifies 12 loci influencing human reproductive behavior

Nicola Barban, Rick Jansen, Ronald de Vlaming, Ahmad Vaez, Jornt J Mandemakers, Felix C Tropf, Xia Shen, James F Wilson, Daniel I Chasman, Ilja M Nolte, Vinicius Tragante, Sander W van der Laan, John R B Perry, Augustine Kong, Tarunveer S Ahluwalia, Eva Albrecht, Laura Yerges-Armstrong, Gil Atzmon, Kirsi Auro, Kristin AyersAndrew Bakshi, Danny Ben-Avraham, Klaus Berger, Aviv Bergman, Lars Bertram, Lawrence F Bielak, Gyda Bjornsdottir, Marc Jan Bonder, Linda Broer, Minh Bui, Caterina Barbieri, Alana Cavadino, Jorge E Chavarro, Constance Turman, Maria Pina Concas, Heather J Cordell, Gail Davies, Peter Eibich, Nicholas Eriksson, Tõnu Esko, Joel Eriksson, Fahimeh Falahi, Janine F Felix, Mark Alan Fontana, Lude Franke, Ilaria Gandin, Audrey J Gaskins, Christian Gieger, Genevieve Lachance, Tim D Spector, BIOS Consortium

Twin Research & Genetic Epidemiology

Research output: Contribution to journal › Article › peer-review

184 Citations (Scopus)

Abstract

The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits.

Original language	English
Pages (from-to)	1462-1472
Number of pages	11
Journal	Nature Genetics
Volume	48
Issue number	12
Early online date	31 Oct 2016
DOIs	https://doi.org/10.1038/ng.3698
Publication status	Published - Dec 2016

Keywords

Birth Order
Female
Fertility
Genome-Wide Association Study
Humans
Maternal Age
Parity
Phenotype
Polymorphism, Single Nucleotide
Pregnancy
Quantitative Trait Loci
Reproduction
Reproductive Behavior
Journal Article

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10.1038/ng.3698

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Barban, N., Jansen, R., de Vlaming, R., Vaez, A., Mandemakers, J. J., Tropf, F. C., Shen, X., Wilson, J. F., Chasman, D. I., Nolte, I. M., Tragante, V., van der Laan, S. W., Perry, J. R. B., Kong, A., Ahluwalia, T. S., Albrecht, E., Yerges-Armstrong, L., Atzmon, G., Auro, K., ... BIOS Consortium (2016). Genome-wide analysis identifies 12 loci influencing human reproductive behavior. Nature Genetics, 48(12), 1462-1472. https://doi.org/10.1038/ng.3698

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title = "Genome-wide analysis identifies 12 loci influencing human reproductive behavior",

abstract = "The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits.",

keywords = "Birth Order, Female, Fertility, Genome-Wide Association Study, Humans, Maternal Age, Parity, Phenotype, Polymorphism, Single Nucleotide, Pregnancy, Quantitative Trait Loci, Reproduction, Reproductive Behavior, Journal Article",

author = "Nicola Barban and Rick Jansen and {de Vlaming}, Ronald and Ahmad Vaez and Mandemakers, {Jornt J} and Tropf, {Felix C} and Xia Shen and Wilson, {James F} and Chasman, {Daniel I} and Nolte, {Ilja M} and Vinicius Tragante and {van der Laan}, {Sander W} and Perry, {John R B} and Augustine Kong and Ahluwalia, {Tarunveer S} and Eva Albrecht and Laura Yerges-Armstrong and Gil Atzmon and Kirsi Auro and Kristin Ayers and Andrew Bakshi and Danny Ben-Avraham and Klaus Berger and Aviv Bergman and Lars Bertram and Bielak, {Lawrence F} and Gyda Bjornsdottir and Bonder, {Marc Jan} and Linda Broer and Minh Bui and Caterina Barbieri and Alana Cavadino and Chavarro, {Jorge E} and Constance Turman and Concas, {Maria Pina} and Cordell, {Heather J} and Gail Davies and Peter Eibich and Nicholas Eriksson and T{\~o}nu Esko and Joel Eriksson and Fahimeh Falahi and Felix, {Janine F} and Fontana, {Mark Alan} and Lude Franke and Ilaria Gandin and Gaskins, {Audrey J} and Christian Gieger and Genevieve Lachance and Spector, {Tim D} and {BIOS Consortium}",

year = "2016",

month = dec,

doi = "10.1038/ng.3698",

language = "English",

volume = "48",

pages = "1462--1472",

journal = "Nature Genetics",

issn = "1061-4036",

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Barban, N, Jansen, R, de Vlaming, R, Vaez, A, Mandemakers, JJ, Tropf, FC, Shen, X, Wilson, JF, Chasman, DI, Nolte, IM, Tragante, V, van der Laan, SW, Perry, JRB, Kong, A, Ahluwalia, TS, Albrecht, E, Yerges-Armstrong, L, Atzmon, G, Auro, K, Ayers, K, Bakshi, A, Ben-Avraham, D, Berger, K, Bergman, A, Bertram, L, Bielak, LF, Bjornsdottir, G, Bonder, MJ, Broer, L, Bui, M, Barbieri, C, Cavadino, A, Chavarro, JE, Turman, C, Concas, MP, Cordell, HJ, Davies, G, Eibich, P, Eriksson, N, Esko, T, Eriksson, J, Falahi, F, Felix, JF, Fontana, MA, Franke, L, Gandin, I, Gaskins, AJ, Gieger, C, Lachance, G , Spector, TD & BIOS Consortium 2016, 'Genome-wide analysis identifies 12 loci influencing human reproductive behavior', Nature Genetics, vol. 48, no. 12, pp. 1462-1472. https://doi.org/10.1038/ng.3698

TY - JOUR

T1 - Genome-wide analysis identifies 12 loci influencing human reproductive behavior

AU - Barban, Nicola

AU - Jansen, Rick

AU - de Vlaming, Ronald

AU - Vaez, Ahmad

AU - Mandemakers, Jornt J

AU - Tropf, Felix C

AU - Shen, Xia

AU - Wilson, James F

AU - Chasman, Daniel I

AU - Nolte, Ilja M

AU - Tragante, Vinicius

AU - van der Laan, Sander W

AU - Perry, John R B

AU - Kong, Augustine

AU - Ahluwalia, Tarunveer S

AU - Albrecht, Eva

AU - Yerges-Armstrong, Laura

AU - Atzmon, Gil

AU - Auro, Kirsi

AU - Ayers, Kristin

AU - Bakshi, Andrew

AU - Ben-Avraham, Danny

AU - Berger, Klaus

AU - Bergman, Aviv

AU - Bertram, Lars

AU - Bielak, Lawrence F

AU - Bjornsdottir, Gyda

AU - Bonder, Marc Jan

AU - Broer, Linda

AU - Bui, Minh

AU - Barbieri, Caterina

AU - Cavadino, Alana

AU - Chavarro, Jorge E

AU - Turman, Constance

AU - Concas, Maria Pina

AU - Cordell, Heather J

AU - Davies, Gail

AU - Eibich, Peter

AU - Eriksson, Nicholas

AU - Esko, Tõnu

AU - Eriksson, Joel

AU - Falahi, Fahimeh

AU - Felix, Janine F

AU - Fontana, Mark Alan

AU - Franke, Lude

AU - Gandin, Ilaria

AU - Gaskins, Audrey J

AU - Gieger, Christian

AU - Lachance, Genevieve

AU - Spector, Tim D

AU - BIOS Consortium

PY - 2016/12

Y1 - 2016/12

N2 - The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits.

AB - The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits.

KW - Birth Order

KW - Female

KW - Fertility

KW - Genome-Wide Association Study

KW - Humans

KW - Maternal Age

KW - Parity

KW - Phenotype

KW - Polymorphism, Single Nucleotide

KW - Pregnancy

KW - Quantitative Trait Loci

KW - Reproduction

KW - Reproductive Behavior

KW - Journal Article

U2 - 10.1038/ng.3698

DO - 10.1038/ng.3698

M3 - Article

C2 - 27798627

SN - 1061-4036

VL - 48

SP - 1462

EP - 1472

JO - Nature Genetics

JF - Nature Genetics

IS - 12

ER -

Genome-wide analysis identifies 12 loci influencing human reproductive behavior

Abstract

Keywords

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