SES-of-Origin and BMI in youth:Comparing Germany and Minnesota

peer reviewe

Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder

Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n similar to 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders

All SNPs are not created equal: genome-wide association studies reveal a consistent pattern of enrichment among functionally annotated SNPs

Recent results indicate that genome-wide association studies (GWAS) have the potential to explain much of the heritability of common complex phenotypes, but methods are lacking to reliably identify the remaining associated single nucleotide polymorphisms (SNPs). We applied stratified False Discovery Rate (sFDR) methods to leverage genic enrichment in GWAS summary statistics data to uncover new loci likely to replicate in independent samples. Specifically, we use linkage disequilibrium-weighted annotations for each SNP in combination with nominal p-values to estimate the True Discovery Rate (TDR = 1−FDR) for strata determined by different genic categories. We show a consistent pattern of enrichment of polygenic effects in specific annotation categories across diverse phenotypes, with the greatest enrichment for SNPs tagging regulatory and coding genic elements, little enrichment in introns, and negative enrichment for intergenic SNPs. Stratified enrichment directly leads to increased TDR for a given p-value, mirrored by increased replication rates in independent samples. We show this in independent Crohn's disease GWAS, where we find a hundredfold variation in replication rate across genic categories. Applying a well-established sFDR methodology we demonstrate the utility of stratification for improving power of GWAS in complex phenotypes, with increased rejection rates from 20% in height to 300% in schizophrenia with traditional FDR and sFDR both fixed at 0.05. Our analyses demonstrate an inherent stratification among GWAS SNPs with important conceptual implications that can be leveraged by statistical methods to improve the discovery of loci

Autism spectrum disorders in adolescence and adulthood: Long-term outcomes and relevant issues for treatment and research

The advances in research and treatment of autism spectrum disorders (ASD) over the past three decades have focused largely on early childhood and school-age years. Although ASD is a lifelong condition, there has been relatively little attention paid to ASD during the adolescent and adulthood periods. As the population of those with ASD continues to rise and age, the need to provide research and treatment for this group has become increasingly evident. This paper reviews the current literature available on symptoms, functioning, and treatment of adolescents and adults with ASD, as well as the unique issues that arise for individuals with ASD after childhood. Adulthood outcomes for ASD are generally poor, even for those with average to above average cognitive ability. Further research and additional clinical resources are needed for this rapidly increasing group

Adolescents of the U.S. National Longitudinal Lesbian Family Study: Sexual Orientation, Sexual Behavior, and Sexual Risk Exposure

This study assessed Kinsey self-ratings and lifetime sexual experiences of 17-year-olds whose lesbian mothers enrolled before these offspring were born in the longest-running, prospective study of same-sex parented families, with a 93% retention rate to date. Data for the current report were gathered through online questionnaires completed by 78 adolescent offspring (39 girls and 39 boys). The adolescents were asked if they had ever been abused and, if so, to specify by whom and the type of abuse (verbal, emotional, physical, or sexual). They were also asked to specify their sexual identity on the Kinsey scale, between exclusively heterosexual and exclusively homosexual. Lifetime sexual behavior was assessed through questions about heterosexual and same-sex contact, age of first sexual experience, contraception use, and pregnancy. The results revealed that there were no reports of physical or sexual victimization by a parent or other caregiver. Regarding sexual orientation, 18.9% of the adolescent girls and 2.7% of the adolescent boys self-rated in the bisexual spectrum, and 0% of girls and 5.4% of boys self-rated as predominantly-to-exclusively homosexual. When compared with age- and gender-matched adolescents of the National Survey of Family Growth, the study offspring were significantly older at the time of their first heterosexual contact, and the daughters of lesbian mothers were significantly more likely to have had same-sex contact. These findings suggest that adolescents reared in lesbian families are less likely than their peers to be victimized by a parent or other caregiver, and that daughters of lesbian mothers are more likely to engage in same-sex behavior and to identify as bisexual

Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.

International audienceWe conducted a combined genome-wide association study (GWAS) of 7,481 individuals with bipolar disorder (cases) and 9,250 controls as part of the Psychiatric GWAS Consortium. Our replication study tested 34 SNPs in 4,496 independent cases with bipolar disorder and 42,422 independent controls and found that 18 of 34 SNPs had P < 0.05, with 31 of 34 SNPs having signals with the same direction of effect (P = 3.8 × 10(-7)). An analysis of all 11,974 bipolar disorder cases and 51,792 controls confirmed genome-wide significant evidence of association for CACNA1C and identified a new intronic variant in ODZ4. We identified a pathway comprised of subunits of calcium channels enriched in bipolar disorder association intervals. Finally, a combined GWAS analysis of schizophrenia and bipolar disorder yielded strong association evidence for SNPs in CACNA1C and in the region of NEK4-ITIH1-ITIH3-ITIH4. Our replication results imply that increasing sample sizes in bipolar disorder will confirm many additional loci

Synthesis of N-succinimidyl-4-[76Br]bromobenzoate and its use in labeling of amino-containing macromolecules

N-succinimidyl-4-[76Br]bromobenzoate was prepd. and incorporated as labeling agent into DNA and bovine serum albumin and chromogranin. [on SciFinder(R)]</p