TY - JOUR
T1 - CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits
AU - LOLIPOP study
AU - Macé, Aurélien
AU - Tuke, Marcus A
AU - Deelen, Patrick
AU - Kristiansson, Kati
AU - Mattsson, Hannele
AU - Nõukas, Margit
AU - Sapkota, Yadav
AU - Schick, Ursula
AU - Porcu, Eleonora
AU - Rüeger, Sina
AU - McDaid, Aaron F
AU - Porteous, David
AU - Winkler, Thomas W
AU - Salvi, Erika
AU - Shrine, Nick
AU - Liu, Xueping
AU - Ang, Wei Q
AU - Zhang, Weihua
AU - Feitosa, Mary F
AU - Venturini, Cristina
AU - van der Most, Peter J
AU - Rosengren, Anders
AU - Wood, Andrew R
AU - Beaumont, Robin N
AU - Jones, Samuel E
AU - Ruth, Katherine S
AU - Yaghootkar, Hanieh
AU - Tyrrell, Jessica
AU - Havulinna, Aki S
AU - Boers, Harmen
AU - Mägi, Reedik
AU - Kriebel, Jennifer
AU - Müller-Nurasyid, Martina
AU - Perola, Markus
AU - Nieminen, Markku
AU - Lokki, Marja-Liisa
AU - Kähönen, Mika
AU - Viikari, Jorma S
AU - Geller, Frank
AU - Lahti, Jari
AU - Palotie, Aarno
AU - Koponen, Päivikki
AU - Lundqvist, Annamari
AU - Rissanen, Harri
AU - Bottinger, Erwin P
AU - Afaq, Saima
AU - Wojczynski, Mary K
AU - Lenzini, Petra
AU - Nolte, Ilja M
AU - Sparsø, Thomas
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - There are few examples of robust associations between rare copy number variants (CNVs) and complex continuous human traits. Here we present a large-scale CNV association meta-analysis on anthropometric traits in up to 191,161 adult samples from 26 cohorts. The study reveals five CNV associations at 1q21.1, 3q29, 7q11.23, 11p14.2, and 18q21.32 and confirms two known loci at 16p11.2 and 22q11.21, implicating at least one anthropometric trait. The discovered CNVs are recurrent and rare (0.01-0.2%), with large effects on height (>2.4 cm), weight (>5 kg), and body mass index (BMI) (>3.5 kg/m2). Burden analysis shows a 0.41 cm decrease in height, a 0.003 increase in waist-to-hip ratio and increase in BMI by 0.14 kg/m2 for each Mb of total deletion burden (P = 2.5 × 10-10, 6.0 × 10-5, and 2.9 × 10-3). Our study provides evidence that the same genes (e.g., MC4R, FIBIN, and FMO5) harbor both common and rare variants affecting body size and that anthropometric traits share genetic loci with developmental and psychiatric disorders.
AB - There are few examples of robust associations between rare copy number variants (CNVs) and complex continuous human traits. Here we present a large-scale CNV association meta-analysis on anthropometric traits in up to 191,161 adult samples from 26 cohorts. The study reveals five CNV associations at 1q21.1, 3q29, 7q11.23, 11p14.2, and 18q21.32 and confirms two known loci at 16p11.2 and 22q11.21, implicating at least one anthropometric trait. The discovered CNVs are recurrent and rare (0.01-0.2%), with large effects on height (>2.4 cm), weight (>5 kg), and body mass index (BMI) (>3.5 kg/m2). Burden analysis shows a 0.41 cm decrease in height, a 0.003 increase in waist-to-hip ratio and increase in BMI by 0.14 kg/m2 for each Mb of total deletion burden (P = 2.5 × 10-10, 6.0 × 10-5, and 2.9 × 10-3). Our study provides evidence that the same genes (e.g., MC4R, FIBIN, and FMO5) harbor both common and rare variants affecting body size and that anthropometric traits share genetic loci with developmental and psychiatric disorders.
KW - Anthropometry
KW - Body Height/genetics
KW - Body Mass Index
KW - Body Size/genetics
KW - Body Weight/genetics
KW - Chromosomes, Human, Pair 1/genetics
KW - Chromosomes, Human, Pair 11/genetics
KW - Chromosomes, Human, Pair 16/genetics
KW - Chromosomes, Human, Pair 18/genetics
KW - Chromosomes, Human, Pair 22/genetics
KW - Chromosomes, Human, Pair 3/genetics
KW - Chromosomes, Human, Pair 7/genetics
KW - DNA Copy Number Variations
KW - Genome-Wide Association Study
KW - Genotype
KW - Humans
KW - Phenotype
KW - Waist-Hip Ratio
KW - White People/genetics
UR - http://www.scopus.com/inward/record.url?scp=85030331328&partnerID=8YFLogxK
U2 - 10.1038/s41467-017-00556-x
DO - 10.1038/s41467-017-00556-x
M3 - Article
C2 - 28963451
AN - SCOPUS:85030331328
SN - 2041-1723
VL - 8
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 744
ER -