|
|
| PMID |
|
|
| TITLE |
|
| Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour. |
|
| ABSTRACT |
|
|
|
| Age at first sexual intercourse and age at first birth have implications for health and evolutionary fitness. In this genome-wide association study (age at first sexual intercourse, N = 387,338; age at first birth, N = 542,901), we identify 371 single-nucleotide polymorphisms, 11 sex-specific, with a 5-6% polygenic score prediction. Heritability of age at first birth shifted from 9% [CI = 4-14%] for women born in 1940 to 22% [CI = 19-25%] for those born in 1965. Signals are driven by the genetics of reproductive biology and externalising behaviour, with key genes related to follicle stimulating hormone (FSHB), implantation (ESR1), infertility and spermatid differentiation. Our findings suggest that polycystic ovarian syndrome may lead to later age at first birth, linking with infertility. Late age at first birth is associated with parental longevity and reduced incidence of type 2 diabetes and cardiovascular disease. Higher childhood socioeconomic circumstances and those in the highest polygenic score decile (90%+) experience markedly later reproductive onset. Results are relevant for improving teenage and late-life health, understanding longevity and guiding experimentation into mechanisms of infertility. |
| © 2021. The Author(s), under exclusive licence to Springer Nature Limited. |
|
| DATE PUBLISHED |
|
|
| HISTORY |
|
| PUBSTATUS |
PUBSTATUSDATE |
| received |
2020/06/05 |
| accepted |
2021/05/14 |
| pubmed |
2021/07/03 06:00 |
| medline |
2021/07/03 06:00 |
| entrez |
2021/07/02 06:30 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Mills MC |
|
Mills |
Melinda C |
MC |
|
Nuffield College, University of Oxford, Oxford, United Kingdom. melinda.mills@nuffield.ox.ac.uk. |
| Tropf FC |
|
Tropf |
Felix C |
FC |
|
Center for Research in Economics and Statistics (CREST), Paris, France. |
| Brazel DM |
|
Brazel |
David M |
DM |
|
Nuffield College, University of Oxford, Oxford, United Kingdom. |
| van Zuydam N |
|
van Zuydam |
Natalie |
N |
|
The Beijer Laboratory and Department of Immunology, Genetics and Pathology, Uppsala University and SciLifeLab, Uppsala, Sweden. |
| Vaez A |
|
Vaez |
Ahmad |
A |
|
Department of Bioinformatics, Isfahan University of Medical Sciences, Isfahan, Iran. |
|
eQTLGen Consortium |
|
|
|
|
|
|
BIOS Consortium |
|
|
|
|
|
|
Human Reproductive Behaviour Consortium |
|
|
|
|
|
| Pers TH |
|
Pers |
Tune H |
TH |
|
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. |
| Snieder H |
|
Snieder |
Harold |
H |
|
Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. |
| Perry JRB |
|
Perry |
John R B |
JRB |
|
MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom. |
| Ong KK |
|
Ong |
Ken K |
KK |
|
MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom. |
| den Hoed M |
|
den Hoed |
Marcel |
M |
|
The Beijer Laboratory and Department of Immunology, Genetics and Pathology, Uppsala University and SciLifeLab, Uppsala, Sweden. |
| Barban N |
|
Barban |
Nicola |
N |
|
Department of Statistical Sciences, University of Bologna, Bologna, Italy. |
| Day FR |
|
Day |
Felix R |
FR |
|
MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom. felix.day@mrc-epid.cam.ac.uk. |
|
| INVESTIGATORS |
|
| LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
| Agbessi |
Mawussé |
M |
|
| Ahsan |
Habibul |
H |
|
| Alves |
Isabel |
I |
|
| Andiappan |
Anand Kumar |
AK |
|
| Arindrarto |
Wibowo |
W |
|
| Awadalla |
Philip |
P |
|
| Battle |
Alexis |
A |
|
| Beutner |
Frank |
F |
|
| Jan Bonder |
Marc |
M |
|
| Boomsma |
Dorret I |
DI |
|
| Christiansen |
Mark W |
MW |
|
| Claringbould |
Annique |
A |
|
| Deelen |
Patrick |
P |
|
| Esko |
Tõnu |
T |
|
| Favé |
Marie-Julie |
MJ |
|
| Franke |
Lude |
L |
|
| Frayling |
Timothy |
T |
|
| Gharib |
Sina A |
SA |
|
| Gibson |
Greg |
G |
|
| Heijmans |
Bastiaan T |
BT |
|
| Hemani |
Gibran |
G |
|
| Jansen |
Rick |
R |
|
| Kähönen |
Mika |
M |
|
| Kalnapenkis |
Anette |
A |
|
| Kasela |
Silva |
S |
|
| Kettunen |
Johannes |
J |
|
| Kim |
Yungil |
Y |
|
| Kirsten |
Holger |
H |
|
| Kovacs |
Peter |
P |
|
| Krohn |
Knut |
K |
|
| Kronberg |
Jaanika |
J |
|
| Kukushkina |
Viktorija |
V |
|
| Kutalik |
Zoltan |
Z |
|
| Lee |
Bernett |
B |
|
| Lehtimäki |
Terho |
T |
|
| Loeffler |
Markus |
M |
|
| Marigorta |
Urko M |
UM |
|
| Mei |
Hailang |
H |
|
| Milani |
Lili |
L |
|
| Montgomery |
Grant W |
GW |
|
| Müller-Nurasyid |
Martina |
M |
|
| Nauck |
Matthias |
M |
|
| Nivard |
Michel G |
MG |
|
| Penninx |
Brenda W J H |
BWJH |
|
| Perola |
Markus |
M |
|
| Pervjakova |
Natalia |
N |
|
| Pierce |
Brandon L |
BL |
|
| Powell |
Joseph |
J |
|
| Prokisch |
Holger |
H |
|
| Psaty |
Bruce M |
BM |
|
| Raitakari |
Olli T |
OT |
|
| Ripatti |
Samuli |
S |
|
| Rotzschke |
Olaf |
O |
|
| Rüeger |
Sina |
S |
|
| Saha |
Ashis |
A |
|
| Scholz |
Markus |
M |
|
| Schramm |
Katharina |
K |
|
| Seppälä |
Ilkka |
I |
|
| Slagboom |
Eline P |
EP |
|
| Stehouwer |
Coen D A |
CDA |
|
| Stumvoll |
Michael |
M |
|
| Sullivan |
Patrick |
P |
|
| 't Hoen |
Peter A C |
PAC |
|
| Teumer |
Alexander |
A |
|
| Thiery |
Joachim |
J |
|
| Tong |
Lin |
L |
|
| Tönjes |
Anke |
A |
|
| van Dongen |
Jenny |
J |
|
| van Iterson |
Maarten |
M |
|
| van Meurs |
Joyce |
J |
|
| Veldink |
Jan H |
JH |
|
| Verlouw |
Joost |
J |
|
| Visscher |
Peter M |
PM |
|
| Völker |
Uwe |
U |
|
| Võsa |
Urmo |
U |
|
| Westra |
Harm-Jan |
HJ |
|
| Wijmenga |
Cisca |
C |
|
| Yaghootkar |
Hanieh |
H |
|
| Yang |
Jian |
J |
|
| Zeng |
Biao |
B |
|
| Zhang |
Futao |
F |
|
| Heijmans |
Bastiaan T |
BT |
|
| 't Hoen |
Peter A C |
PAC |
|
| van Meurs |
Joyce |
J |
|
| Isaacs |
Aaron |
A |
|
| Jansen |
Rick |
R |
|
| Franke |
Lude |
L |
|
| Boomsma |
Dorret I |
DI |
|
| Pool |
René |
R |
|
| van Dongen |
Jenny |
J |
|
| Jan Hottenga |
Jouke |
J |
|
| van Greevenbroek |
Marleen M J |
MMJ |
|
| Stehouwer |
Coen D A |
CDA |
|
| van der Kallen |
Carla J H |
CJH |
|
| Schalkwijk |
Casper G |
CG |
|
| Wijmenga |
Cisca |
C |
|
| Franke |
Lude |
L |
|
| Zhernakova |
Sasha |
S |
|
| Tigchelaar |
Ettje F |
EF |
|
| Slagboom |
Eline P |
EP |
|
| Beekman |
Marian |
M |
|
| Deelen |
Joris |
J |
|
| van Heemst |
Diana |
D |
|
| Veldink |
Jan H |
JH |
|
| van den Berg |
Leonard H |
LH |
|
| van Duijn |
Cornelia M |
CM |
|
| Hofman |
Bert A |
BA |
|
| Isaacs |
Aaron |
A |
|
| Uitterlinden |
André G |
AG |
|
| van Meurs |
Joyce |
J |
|
| Jhamai |
P Mila |
PM |
|
| Verbiest |
Michael |
M |
|
| Suchiman |
H Eka D |
HED |
|
| Verkerk |
Marijn |
M |
|
| van der Breggen |
Ruud |
R |
|
| van Rooij |
Jeroen |
J |
|
| Lakenberg |
Nico |
N |
|
| Mei |
Hailiang |
H |
|
| van Iterson |
Maarten |
M |
|
| van Galen |
Michiel |
M |
|
| Bot |
Jan |
J |
|
| Zhernakova |
Dasha V |
DV |
|
| Jansen |
Rick |
R |
|
| van 't Hof |
Peter |
P |
|
| Deelen |
Patrick |
P |
|
| Nooren |
Irene |
I |
|
| 't Hoen |
Peter A C |
PAC |
|
| Heijmans |
Bastiaan T |
BT |
|
| Moed |
Matthijs |
M |
|
| Franke |
Lude |
L |
|
| Vermaat |
Martijn |
M |
|
| Zhernakova |
Dasha V |
DV |
|
| Luijk |
René |
R |
|
| Jan Bonder |
Marc |
M |
|
| van Iterson |
Maarten |
M |
|
| Deelen |
Patrick |
P |
|
| van Dijk |
Freerk |
F |
|
| van Galen |
Michiel |
M |
|
| Arindrarto |
Wibowo |
W |
|
| Kielbasa |
Szymon M |
SM |
|
| Swertz |
Morris A |
MA |
|
| van Zwet |
Erik W |
EW |
|
| Jansen |
Rick |
R |
|
| 't Hoen |
Peter A C |
PAC |
|
| Heijmans |
Bastiaan T |
BT |
|
| Akimova |
Evelina T |
ET |
|
| Bergmann |
Sven |
S |
|
| Boardman |
Jason D |
JD |
|
| Boomsma |
Dorret I |
DI |
|
| Brumat |
Marco |
M |
|
| Buring |
Julie E |
JE |
|
| Cesarini |
David |
D |
|
| Chasman |
Daniel I |
DI |
|
| Chavarro |
Jorge E |
JE |
|
| Cocca |
Massimiliano |
M |
|
| Concas |
Maria Pina |
MP |
|
| Davey-Smith |
George |
G |
|
| Davies |
Gail |
G |
|
| Deary |
Ian J |
IJ |
|
| Esko |
Tõnu |
T |
|
| Franco |
Oscar |
O |
|
| Gaskins |
Audrey J |
AJ |
|
| de Geus |
Eco J C |
EJC |
|
| Gieger |
Christian |
C |
|
| Girotto |
Giorgia |
G |
|
| Grabe |
Hans Jörgen |
HJ |
|
| Gunderson |
Erica P |
EP |
|
| Harris |
Kathleen Mullan |
KM |
|
| Hartwig |
Fernando P |
FP |
|
| He |
Chunyan |
C |
|
| van Heemst |
Diana |
D |
|
| Hill |
W David |
WD |
|
| Homuth |
Georg |
G |
|
| Horta |
Bernando Lessa |
BL |
|
| Jan Hottenga |
Jouke |
J |
|
| Huang |
Hongyang |
H |
|
| Hyppӧnen |
Elina |
E |
|
| Ikram |
M Arfan |
MA |
|
| Jansen |
Rick |
R |
|
| Johannesson |
Magnus |
M |
|
| Kamali |
Zoha |
Z |
|
| Kavousi |
Maryam |
M |
|
| Kraft |
Peter |
P |
|
| Kühnel |
Brigitte |
B |
|
| Langenberg |
Claudia |
C |
|
| Lind |
Penelope A |
PA |
|
| Luan |
Jian'an |
J |
|
| Mägi |
Reedik |
R |
|
| Magnusson |
Patrik K E |
PKE |
|
| Mahajan |
Anubha |
A |
|
| Martin |
Nicholas G |
NG |
|
| Mbarek |
Hamdi |
H |
|
| McCarthy |
Mark I |
MI |
|
| McMahon |
George |
G |
|
| McQueen |
Matthew B |
MB |
|
| Medland |
Sarah E |
SE |
|
| Meitinger |
Thomas |
T |
|
| Metspalu |
Andres |
A |
|
| Mihailov |
Evelin |
E |
|
| Milani |
Lili |
L |
|
| Missmer |
Stacey A |
SA |
|
| Møllegaard |
Stine |
S |
|
| Mook-Kanamori |
Dennis O |
DO |
|
| Morgan |
Anna |
A |
|
| van der Most |
Peter J |
PJ |
|
| de Mutsert |
Renée |
R |
|
| Nauck |
Matthias |
M |
|
| Nolte |
Ilja M |
IM |
|
| Noordam |
Raymond |
R |
|
| Penninx |
Brenda W J H |
BWJH |
|
| Peters |
Annette |
A |
|
| Power |
Chris |
C |
|
| Redmond |
Paul |
P |
|
| Rich-Edwards |
Janet W |
JW |
|
| Ridker |
Paul M |
PM |
|
| Rietveld |
Cornelius A |
CA |
|
| Ring |
Susan M |
SM |
|
| Rose |
Lynda M |
LM |
|
| Rueedi |
Rico |
R |
|
| Stefánsson |
Kári |
K |
|
| Stöckl |
Doris |
D |
|
| Strauch |
Konstantin |
K |
|
| Swertz |
Morris A |
MA |
|
| Teumer |
Alexander |
A |
|
| Thorleifsson |
Gudmar |
G |
|
| Thorsteinsdottir |
Unnur |
U |
|
| Thurik |
A Roy |
AR |
|
| Timpson |
Nicholas J |
NJ |
|
| Turman |
Constance |
C |
|
| Uitterlinden |
André G |
AG |
|
| Waldenberger |
Melanie |
M |
|
| Wareham |
Nicholas J |
NJ |
|
| Willemsen |
Gonneke |
G |
|
| Zhao |
Jing Hau |
JH |
|
|
| JOURNAL |
|
| VOLUME: |
| ISSUE: |
| TITLE: Nature human behaviour |
| ISOABBREVIATION: Nat Hum Behav |
| YEAR: 2021 |
| MONTH: Jul |
| DAY: 01 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 2397-3374 |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
|
| MEDLINETA: Nat Hum Behav |
| COUNTRY: England |
| ISSNLINKING: 2397-3374 |
| NLMUNIQUEID: 101697750 |
|
| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Journal Article |
|
| COMMENTS AND CORRECTIONS |
|
| REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
| ErratumIn |
Nat Hum Behav. 2021 Jul 28;: |
34321615 |
|
|
| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| 615603 |
EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)) |
|
| 835079 |
EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) |
|
| ES/N011856/1 |
RCUK | Economic and Social Research Council (ESRC) |
|
| Centre for Demographic Science |
Leverhulme Trust |
|
| Centre Demographic Science |
Leverhulme Trust |
|
|
| GENERAL NOTE |
|
|
| KEYWORDS |
|
|
| MESH HEADINGS |
|
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
|
| OTHER ID's |
|
|
|
