Common body mass index-associated variants confer risk of extreme obesity

被引：83

作者：

Cotsapas, Chris ^{[1
,3
,4
]}

Speliotes, Elizabeth K. ^{[1
,5
,6
]}

Hatoum, Ida J. ^{[2
,5
]}

Greenawalt, Danielle M. ^{[7
]}

Dobrin, Radu ^{[7
]}

Lum, Pek Y. ^{[7
]}

Suver, Christine ^{[7
]}

Chudin, Eugene

Kemp, Daniel ^{[8
]}

Reitman, Marc ^{[8
]}

Voight, Benjamin F. ^{[1
,3
,4
]}

Neale, Benjamin M. ^{[1
,3
,4
]}

Schadt, Eric E.

Hirschhorn, Joel N. ^{[1
,6
,9
,10
,11
]}

Kaplan, Lee M. ^{[2
,5
]}

Daly, Mark J. ^{[1
,3
,4
]}

机构：

[1] Harvard Univ, Sch Med, Dept Med, Boston, MA USA

[2] Massachusetts Gen Hosp, MGH Weight Ctr, Boston, MA 02114 USA

[3] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[4] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA

[5] MIT & Harvard, Broad Inst, Metab Initiat, Cambridge, MA USA

[6] MIT & Harvard, Broad Inst, Med & Populat Genet Program, Cambridge, MA USA

[7] Genet Rosetta Inpharmat LLC, Seattle, WA 98109 USA

[8] Merck Res Labs, Dept Metab Disorders, Rahway, NJ 07065 USA

[9] Childrens Hosp, Program Genom, Boston, MA 02115 USA

[10] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA

[11] Childrens Hosp, Div Genet, Boston, MA 02115 USA

来源：

HUMAN MOLECULAR GENETICS | 2009年 / 18卷 / 18期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; EARLY-ONSET; FTO GENE; STRATIFICATION; CHILDHOOD; LOCI;

D O I：

10.1093/hmg/ddp292

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

To investigate the genetic architecture of severe obesity, we performed a genome-wide association study of 775 cases and 3197 unascertained controls at similar to 550 000 markers across the autosomal genome. We found convincing association to the previously described locus including the FTO gene. We also found evidence of association at a further six of 12 other loci previously reported to influence body mass index (BMI) in the general population and one of three associations to severe childhood and adult obesity and that cases have a higher proportion of risk-conferring alleles than controls. We found no evidence of homozygosity at any locus due to identity-by-descent associating with phenotype which would be indicative of rare, penetrant alleles, nor was there excess genome-wide homozygosity in cases relative to controls. Our results suggest that variants influencing BMI also contribute to severe obesity, a condition at the extreme of the phenotypic spectrum rather than a distinct condition.

引用

页码：3502 / 3507

页数：6

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