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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 2,907 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 datasets. Seventy-six (72 independent) SNPs were taken forward for in silico (two datasets) or de novo (13 datasets) replication genotyping in 2,677 independent AN cases and 8,629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication datasets comprised 5,551 AN cases and 21,080 controls. AN subtype analyses (1,606 AN restricting; 1,445 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 to 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 that 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.

IntroductionHypophosphatasia features selective deficiency of activity of the tissue-nonspecific (liver/bone/kidney) alkaline phosphatase (ALP) To test whether human PALP and TNSALP are physiologically active toward the same substrates, we studied PEA, PPi, and PLP levels during and after pregnancy in three women who are carriers for hypophosphatasia. Hypophosphatasemia corrected during the third trimester because of PALP in maternal blood. Blood or urine concentrations of PEA, PPi, and PLP diminished substantially during that time. After childbirth, maternal circulating levels of PALP decreased, and PEA, PPi, and PLP levels abruptly increased. In serum, unremarkable concentrations of IALP and low levels of TNSALP did not change during the study period.We conclude that PALP, like TNSALP, is physiologically active toward PEA, PPi, and PLP in humans. We speculate from molecular/crystallographic information, indicating significant similarity of structure of the substrate-binding site of ALPs throughout nature, that all ALP isoenzymes recognize these same three phosphocompound substrates.

Objective: The current study investigated associations among eating disorders, depressive symptoms during pregnancy and postpartum, and perfectionism in a population-based sample of women.Method: Females who reported !1 pregnancy (N ¼ 1,119) completed questionnaires assessing perfectionism, eating disorder symptomatology, and depression during pregnancy and postpartum. Information regarding participants' history of major depressive disorder (MDD) was also available from structured psychiatric interviews completed during a previous wave of data collection.Results: Depressive symptoms during pregnancy and postpartum were high among women with a history of eating disorders. Both binge eating disorder (BED) and bulimia nervosa (BN) were positively associated with symptoms of postpartum depression (PPD), even when lifetime MDD was controlled. However, logistic regression indicated that women with a history of BN and BED are at particular risk of developing PPD symptomatology. Linear regression analyses conducted with the subset of the sample who endorsed a PPD screening item suggested that the severity of PPD symptomatology may be attributable to Concern Over Mistakes, a specific aspect of perfectionism. Conclusion:These results highlight the importance of assessing specific features of perfectionism. In addition, they suggest that women with BN, BED, or high Concern over Mistakes may be at particular risk of developing PPD symptoms, and could benefit from prenatal screening. V V C 2006 by Wiley Periodicals, Inc.