View Full Version : I've been saying this for years. . .

02-27-13, 10:54 PM

The study hasn't come out yet, but this article says that a genetic link has been found. I'll be keeping an eye out for more news.

02-27-13, 11:20 PM
I remember reading something about that a while ago (sometime within the last year) and found it quite interesting. I'm curious to see what genes exactly, and if the ones they found seem to be markers for only depression, bipolar disorder, and schizophrenia, where does that leave ADHD and Autism? It didn't mention any marked genes for them, only that they were similar in symptoms.

02-28-13, 04:30 AM
I am so glad you posted this amtram. I just saw this yesterday and I have always thought this to be the case.

02-28-13, 10:08 AM
Raw Story ( has a bit more detail, and Lunacie posted a link to MSN ( that also expanded on it a bit. I've been afraid to Google this for fear of all the bad coverage that's going to be out there and the nasty comments from ADHD deniers, but I suppose I'll have to do it eventually.

I'm hoping that someone like Neuroskeptic or Wiring the Brain or some other neuroscience blog I follow will provide some inside information soon. This hasn't been published yet, and when it is, the full text isn't going to be free!

02-28-13, 10:17 AM
As someone who has a disabling comorbidity this comes as validation. There are commonalities between these disorders and one should not have to give priority to one or the other when it comes to treatment.

02-28-13, 10:26 AM
Yep. I've long believed in shared genes for ADHD, Bipolar, MDD etc.

:| <-- Behold my "not surprised" face.

02-28-13, 11:03 AM
Thanks Amtram!!

Here is the abstract of the study in the Lancet. I could attach the pdf but I'm not sure if it isn't against the guidelines???

The Lancet, Early Online Publication, 28 February 2013
doi:10.1016/S0140-6736(12)62129-1 ( or Link Using DOI (

Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis


Findings from family and twin studies suggest that genetic contributions to psychiatric disorders do not in all cases map to present diagnostic categories. We aimed to identify specific variants underlying genetic effects shared between the five disorders in the Psychiatric Genomics Consortium: autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia.


We analysed genome-wide single-nucleotide polymorphism (SNP) data for the five disorders in 33 332 cases and 27 888 controls of European ancestory. To characterise allelic effects on each disorder, we applied a multinomial logistic regression procedure with model selection to identify the best-fitting model of relations between genotype and phenotype. We examined cross-disorder effects of genome-wide significant loci previously identified for bipolar disorder and schizophrenia, and used polygenic risk-score analysis to examine such effects from a broader set of common variants. We undertook pathway analyses to establish the biological associations underlying genetic overlap for the five disorders. We used enrichment analysis of expression quantitative trait loci (eQTL) data to assess whether SNPs with cross-disorder association were enriched for regulatory SNPs in post-mortem brain-tissue samples.


SNPs at four loci surpassed the cutoff for genome-wide significance (p<5×10−8) in the primary analysis: regions on chromosomes 3p21 and 10q24, and SNPs within two L-type voltage-gated calcium channel subunits, CACNA1C and CACNB2. Model selection analysis supported effects of these loci for several disorders. Loci previously associated with bipolar disorder or schizophrenia had variable diagnostic specificity. Polygenic risk scores showed cross-disorder associations, notably between adult-onset disorders. Pathway analysis supported a role for calcium channel signalling genes for all five disorders. Finally, SNPs with evidence of cross-disorder association were enriched for brain eQTL markers.


Our findings show that specific SNPs are associated with a range of psychiatric disorders of childhood onset or adult onset. In particular, variation in calcium-channel activity genes seems to have pleiotropic effects on psychopathology. These results provide evidence relevant to the goal of moving beyond descriptive syndromes in psychiatry, and towards a nosology informed by disease cause.


National Institute of Mental Health.

02-28-13, 11:12 AM
I could attach the pdf Do you have access to the full-text PDF behind the pay wall?

02-28-13, 11:24 AM
It would be illegal for us to share that, unfortunately.

02-28-13, 11:27 AM
Do you have access to the full-text PDF behind the pay wall?

Yes, I guess my university has a subscription to the journal.

It would be illegal for us to share that, unfortunately.

Yes, I thought so. Sigh. I wish information was made freely accessible to everyone.

02-28-13, 12:17 PM
A live interview with the lead researcher can be viewed at

02-28-13, 01:44 PM
Here's a link to the full text of the Lancet study. It does require registration -- so use that throwaway email address and a name of your choice ;) :

02-28-13, 03:08 PM
Hey! The paper is free if you're registered!

Still can't copy-paste legally, but here are some snippets:

The pathogenic mechanisms of psychiatric disorders are largely unknown, so diagnostic boundaries are difficult to define. Genetic risk factors are important in the causation of all major psychiatric disorders,2 ( and genetic strategies are widely used to assess potential overlaps. The imminent revision of psychiatric classifications in the Diagnostic and Statistical Manual of Mental Disorders (DSM) and the International Classification of Diseases (ICD) has reinvigorated debate about the validity of diagnostic boundaries. With increasing availability of large genome-wide genotype data for several psychiatric disorders, shared cause can now be examined at a molecular level.

From Methods:

Samples and genotypes

The sample for these analyses consisted of cases, controls, and family-based samples assembled for previous genome-wide PGC mega-analyses of individual-level data.6 (, 7 (, 16 (, 17 ( Cases and controls were not related. For the family-based samples, we matched alleles transmitted to affected offspring (trio cases) with untransmitted alleles (pseudocontrols). We estimated the identity-by-descent relation for all pairs of individuals to identify any duplicate individuals in the component datasets. When duplicates were detected, one member of each set was retained. We then randomly allocated these individuals, with a random number generator, to a disorder case-control dataset. Sample sizes differ from previous reports because of this allocation of overlapping individuals. All patients were of European ancestory and met criteria from the DSM third edition revised or fourth edition for the primary disorder of interest.

To ensure comparability between samples, raw genotype and phenotype data for each study were uploaded to a central server and processed through the same quality control, imputation, and analysis process (appendix ( (, 7 ( We analysed imputed SNP dosages from 1 250 922 autosomal SNPs.

From Results:

After correction for multiple testing (appendix pp 14—16 (, we noted significant enrichment for a set of calcium channel activity genes associated with catalysis of facilitated diffusion of calcium ions through a transmembrane calcium channel (appendix p 64 ( With a cutoff of p<10−3, 20 of 67 gene regions in this set were associated in the five-disorder meta-analysis, including voltage-gated calcium-channel subunits CACNA1C, CACNA1D, CACNA1E, CACNA1S, CACNA2D2, CACNA2D4, and CACNB2 (appendix pp 65—66 ( Because calcium-channel genes (mainly CACNA1C) have previously been associated with bipolar disorder, we repeated the pathway analysis with exclusion of the datasets for bipolar disorder and confirmed that enrichment was not dependent on cases with this disorder (data not shown). Appendix pp 69—70 ( depict functional associations between these calcium-channel activity genes on the basis of various lines of evidence.

From Discussion:

Accumulating evidence, including that from clinical, epidemiological, and molecular genetic studies, suggests that some genetic risk factors are shared between neuropsychiatric disorders. Genome-wide studies have identified rare copy-number variants that confer risk of several neuropsychiatric disorders including autism, attention deficit-hyperactivity disorder, epilepsy, intellectual disability, and schizophrenia.39 ( Our analyses of 14 SNPs previously identified as being genome-wide significantly associated with schizophrenia and bipolar disorder suggest that some loci identified in studies of individual disorders have broader phenotypic effects. Our results suggest a diversity of findings, with some SNPs showing diagnostic specificity and others pleiotropic effects on two or more of the five disorders.

and this:

The identification of genetic variants that confer risk of a diverse set of psychiatric disorders parallels findings from other medical specialties. Most notably, GWAS41 (, 42 ( of autoimmune disorders have shown extensive overlap in genetic variants that affect a diverse range of diseases, including rheumatoid arthritis, coeliac disease, multiple sclerosis, systemic lupus erythematosus, psoriasis, Crohn's disease, and type 1 diabetes. Our results provide insights into the shared causation of psychiatric disorders (panel ( In particular, alterations in calcium-channel signalling could represent a fundamental mechanism contributing to a broad vulnerability to psychopathology.

and finally, this:

This analysis provides the first genome-wide evidence that individual and aggregate molecular genetic risk factors are shared between five childhood-onset or adult-onset psychiatric disorders that are treated as distinct categories in clinical practice. As such, our findings are relevant to the goal of moving beyond descriptive syndromes in psychiatry and towards a nosology informed by disease cause. The finding that genetic variants have cross-disorder effects is an empirical step towards helping clinicians understand the common co-occurrence of clinical phenotypes in individual patients. Our results implicate a specific biological pathway—voltage-gated calcium-channel signalling—as a contributor to the pathogenesis of several psychiatric disorders, and support the potential of this pathway as a therapeutic target for psychiatric disease. These results add to literature in several specialties (including autoimmune and metabolic diseases) that have begun to document widespread pleiotropy of genetic risk factors across traditional diagnostic boundaries.

I'm going to spend some more time looking at the details over. . .however long it takes me to get around to it, but I thought these segments would be fairly understandable to most people here.