Nat Commun.: co-auth.: group Reymond

Nat Commun. 2017 Sep 29;8(1):744. doi: 10.1038/s41467-017-00556-x.

CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits.

Macé A1,2,3Tuke MA4Deelen P5,6Kristiansson K7,8Mattsson H7,8Nõukas M9,10Sapkota Y11,12Schick U13Porcu E2,14Rüeger S1,2McDaid AF1,2Porteous D15Winkler TW16Salvi E17Shrine N18Liu X19Ang WQ20Zhang W21,22Feitosa MF23Venturini C24van der Most PJ25Rosengren A26,27Wood AR4Beaumont RN4Jones SE4Ruth KS4Yaghootkar H4Tyrrell J4Havulinna AS7Boers H5,6Mägi R9Kriebel J28,29,30Müller-Nurasyid M31,32,33Perola M7,34Nieminen M35Lokki ML36Kähönen M37,38Viikari JS39,40Geller F19Lahti J41,42Palotie A8,43,44Koponen P7Lundqvist A7Rissanen H7Bottinger EP13Afaq S21Wojczynski MK23Lenzini P23Nolte IM25Sparsø T26,27Schupf N45Christensen K46Perls TT47Newman AB48Werge T26,27,49Snieder H25Spector TD24Chambers JC21,22,50Koskinen S7Melbye M19,51,52Raitakari OT53,54Lehtimäki T55,56Tobin MD18,57Wain LV18,57Sinisalo J35Peters A29,30,33Meitinger T58,59Martin NG60Wray NR61Montgomery GW11,62Medland SE11Swertz MA5,6Vartiainen E7Borodulin K7Männistö S7Murray A4Bochud M1Jacquemont S63,64Rivadeneira F65,66Hansen TF26,27Oldehinkel AJ67Mangino M24,68Province MA23Deloukas P69,70Kooner JS22,50,71Freathy RM4Pennell C20Feenstra B19Strachan DP72Lettre G73,74Hirschhorn J75,76,77Cusi D17,78Heid IM16Hayward C79Männik K9,14Beckmann JS2Loos RJF13,80Nyholt DR11,81Metspalu A9Eriksson JG82,83Weedon MN4Salomaa V7Franke L5Reymond A14Frayling TM4Kutalik Z84,85.


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.Individual SNPs have small effects on anthropometric traits, yet the impact of CNVs has remained largely unknown. Here, Kutalik and co-workers perform a large-scale genome-wide meta-analysis of structural variation and find rare CNVs associated with height, weight and BMI with large effect sizes.

PMID: 28963451