serval:BIB_9700E363D9A2
Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus.
10.1038/nature10406
21881559
000295575400042
Jacquemont
S.
author
Reymond
A.
author
Zufferey
F.
author
Harewood
L.
author
Walters
R.G.
author
Kutalik
Z.
author
Martinet
D.
author
Shen
Y.
author
Valsesia
A.
author
Beckmann
N.D.
author
Thorleifsson
G.
author
Belfiore
M.
author
Bouquillon
S.
author
Campion
D.
author
de Leeuw
N.
author
de Vries
B.B.
author
Esko
T.
author
Fernandez
B.A.
author
Fernández-Aranda
F.
author
Fernández-Real
J.M.
author
Gratacòs
M.
author
Guilmatre
A.
author
Hoyer
J.
author
Jarvelin
M.R.
author
Kooy
R.F.
author
Kurg
A.
author
Le Caignec
C.
author
Männik
K.
author
Platt
O.S.
author
Sanlaville
D.
author
Van Haelst
M.M.
author
Villatoro Gomez
S.
author
Walha
F.
author
Wu
B.L.
author
Yu
Y.
author
Aboura
A.
author
Addor
M.C.
author
Alembik
Y.
author
Antonarakis
S.E.
author
Arveiler
B.
author
Barth
M.
author
Bednarek
N.
author
Béna
F.
author
Bergmann
S.
author
Beri
M.
author
Bernardini
L.
author
Blaumeiser
B.
author
Bonneau
D.
author
Bottani
A.
author
Boute
O.
author
Brunner
H.G.
author
Cailley
D.
author
Callier
P.
author
Chiesa
J.
author
Chrast
J.
author
Coin
L.
author
Coutton
C.
author
Cuisset
J.M.
author
Cuvellier
J.C.
author
David
A.
author
de Freminville
B.
author
Delobel
B.
author
Delrue
M.A.
author
Demeer
B.
author
Descamps
D.
author
Didelot
G.
author
Dieterich
K.
author
Disciglio
V.
author
Doco-Fenzy
M.
author
Drunat
S.
author
Duban-Bedu
B.
author
Dubourg
C.
author
El-Sayed Moustafa
J.S.
author
Elliott
P.
author
Faas
B.H.
author
Faivre
L.
author
Faudet
A.
author
Fellmann
F.
author
Ferrarini
A.
author
Fisher
R.
author
Flori
E.
author
Forer
L.
author
Gaillard
D.
author
Gerard
M.
author
Gieger
C.
author
Gimelli
S.
author
Gimelli
G.
author
Grabe
H.J.
author
Guichet
A.
author
Guillin
O.
author
Hartikainen
A.L.
author
Heron
D.
author
Hippolyte
L.
author
Holder
M.
author
Homuth
G.
author
Isidor
B.
author
Jaillard
S.
author
Jaros
Z.
author
Jiménez-Murcia
S.
author
Helas
G.J.
author
Jonveaux
P.
author
Kaksonen
S.
author
Keren
B.
author
Kloss-Brandstätter
A.
author
Knoers
N.V.
author
Koolen
D.A.
author
Kroisel
P.M.
author
Kronenberg
F.
author
Labalme
A.
author
Landais
E.
author
Lapi
E.
author
Layet
V.
author
Legallic
S.
author
Leheup
B.
author
Leube
B.
author
Lewis
S.
author
Lucas
J.
author
MacDermot
K.D.
author
Magnusson
P.
author
Marshall
C.
author
Mathieu-Dramard
M.
author
McCarthy
M.I.
author
Meitinger
T.
author
Mencarelli
M.A.
author
Merla
G.
author
Moerman
A.
author
Mooser
V.
author
Morice-Picard
F.
author
Mucciolo
M.
author
Nauck
M.
author
Ndiaye
N.C.
author
Nordgren
A.
author
Pasquier
L.
author
Petit
F.
author
Pfundt
R.
author
Plessis
G.
author
Rajcan-Separovic
E.
author
Ramelli
G.P.
author
Rauch
A.
author
Ravazzolo
R.
author
Reis
A.
author
Renieri
A.
author
Richart
C.
author
Ried
J.S.
author
Rieubland
C.
author
Roberts
W.
author
Roetzer
K.M.
author
Rooryck
C.
author
Rossi
M.
author
Saemundsen
E.
author
Satre
V.
author
Schurmann
C.
author
Sigurdsson
E.
author
Stavropoulos
D.J.
author
Stefansson
H.
author
Tengström
C.
author
Thorsteinsdóttir
U.
author
Tinahones
F.J.
author
Touraine
R.
author
Vallée
L.
author
van Binsbergen
E.
author
Van der Aa
N.
author
Vincent-Delorme
C.
author
Visvikis-Siest
S.
author
Vollenweider
P.
author
Völzke
H.
author
Vulto-van Silfhout
A.T.
author
Waeber
G.
author
Wallgren-Pettersson
C.
author
Witwicki
R.M.
author
Zwolinksi
S.
author
Andrieux
J.
author
Estivill
X.
author
Gusella
J.F.
author
Gustafsson
O.
author
Metspalu
A.
author
Scherer
S.W.
author
Stefansson
K.
author
Blakemore
A.I.
author
Beckmann
J.S.
author
Froguel
P.
author
article
2011
Nature
1476-4687
0028-0836
journal
478
7367
97-102
Both obesity and being underweight have been associated with increased mortality. Underweight, defined as a body mass index (BMI) ≤ 18.5 kg per m(2) in adults and ≤ -2 standard deviations from the mean in children, is the main sign of a series of heterogeneous clinical conditions including failure to thrive, feeding and eating disorder and/or anorexia nervosa. In contrast to obesity, few genetic variants underlying these clinical conditions have been reported. We previously showed that hemizygosity of a ∼600-kilobase (kb) region on the short arm of chromosome 16 causes a highly penetrant form of obesity that is often associated with hyperphagia and intellectual disabilities. Here we show that the corresponding reciprocal duplication is associated with being underweight. We identified 138 duplication carriers (including 132 novel cases and 108 unrelated carriers) from individuals clinically referred for developmental or intellectual disabilities (DD/ID) or psychiatric disorders, or recruited from population-based cohorts. These carriers show significantly reduced postnatal weight and BMI. Half of the boys younger than five years are underweight with a probable diagnosis of failure to thrive, whereas adult duplication carriers have an 8.3-fold increased risk of being clinically underweight. We observe a trend towards increased severity in males, as well as a depletion of male carriers among non-medically ascertained cases. These features are associated with an unusually high frequency of selective and restrictive eating behaviours and a significant reduction in head circumference. Each of the observed phenotypes is the converse of one reported in carriers of deletions at this locus. The phenotypes correlate with changes in transcript levels for genes mapping within the duplication but not in flanking regions. The reciprocal impact of these 16p11.2 copy-number variants indicates that severe obesity and being underweight could have mirror aetiologies, possibly through contrasting effects on energy balance.
eng
60_published
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
University of Lausanne
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