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A genome-wide association study of anorexia nervosa.

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Title: A genome-wide association study of anorexia nervosa.
Authors: Boraska, V, Franklin, C S, Floyd, J A B, Thornton, L M, Huckins, L M, Southam, L, Rayner, N W, Tachmazidou, I, Klump, K L, Treasure, J, Lewis, C M, Schmidt, U, Tozzi, F, Kiezebrink, K, Hebebrand, J, Gorwood, P, Adan, R A H, Kas, M J H, Favaro, A, Santonastaso, P
Source: Molecular Psychiatry. Oct2014, Vol. 19 Issue 10, p1085-1094. 10p.
Subjects: Anorexia nervosa, Eating disorders, Pathological psychology, Body mass index, Genomics, Physiology
Abstract: Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10−7) in SOX2OT and rs17030795 (P=5.84 × 10−6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10−6) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10−6) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10−6), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field. [ABSTRACT FROM AUTHOR]
Copyright of Molecular Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: A genome-wide association study of anorexia nervosa.
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  Data: <searchLink fieldCode="AR" term="%22Boraska%2C+V%22">Boraska, V</searchLink><br /><searchLink fieldCode="AR" term="%22Franklin%2C+C+S%22">Franklin, C S</searchLink><br /><searchLink fieldCode="AR" term="%22Floyd%2C+J+A+B%22">Floyd, J A B</searchLink><br /><searchLink fieldCode="AR" term="%22Thornton%2C+L+M%22">Thornton, L M</searchLink><br /><searchLink fieldCode="AR" term="%22Huckins%2C+L+M%22">Huckins, L M</searchLink><br /><searchLink fieldCode="AR" term="%22Southam%2C+L%22">Southam, L</searchLink><br /><searchLink fieldCode="AR" term="%22Rayner%2C+N+W%22">Rayner, N W</searchLink><br /><searchLink fieldCode="AR" term="%22Tachmazidou%2C+I%22">Tachmazidou, I</searchLink><br /><searchLink fieldCode="AR" term="%22Klump%2C+K+L%22">Klump, K L</searchLink><br /><searchLink fieldCode="AR" term="%22Treasure%2C+J%22">Treasure, J</searchLink><br /><searchLink fieldCode="AR" term="%22Lewis%2C+C+M%22">Lewis, C M</searchLink><br /><searchLink fieldCode="AR" term="%22Schmidt%2C+U%22">Schmidt, U</searchLink><br /><searchLink fieldCode="AR" term="%22Tozzi%2C+F%22">Tozzi, F</searchLink><br /><searchLink fieldCode="AR" term="%22Kiezebrink%2C+K%22">Kiezebrink, K</searchLink><br /><searchLink fieldCode="AR" term="%22Hebebrand%2C+J%22">Hebebrand, J</searchLink><br /><searchLink fieldCode="AR" term="%22Gorwood%2C+P%22">Gorwood, P</searchLink><br /><searchLink fieldCode="AR" term="%22Adan%2C+R+A+H%22">Adan, R A H</searchLink><br /><searchLink fieldCode="AR" term="%22Kas%2C+M+J+H%22">Kas, M J H</searchLink><br /><searchLink fieldCode="AR" term="%22Favaro%2C+A%22">Favaro, A</searchLink><br /><searchLink fieldCode="AR" term="%22Santonastaso%2C+P%22">Santonastaso, P</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Molecular+Psychiatry%22">Molecular Psychiatry</searchLink>. Oct2014, Vol. 19 Issue 10, p1085-1094. 10p.
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  Data: Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10−7) in SOX2OT and rs17030795 (P=5.84 × 10−6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10−6) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10−6) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10−6), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Molecular Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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