Thursday, 5 February 2015

Genes and Progression

Akkad DA, Bellenberg B, Esser S, Weiler F, Epplen JT, Gold R, Lukas C, Haghikia A. Multiple sclerosis risk loci correlate with cervical cord atrophy and may explain the course of disability. Neurogenetics. 2015 Jan. [Epub ahead of print]

Genome-wide association studies (GWAS) underscore the genetic basis of multiple sclerosis (MS); however, only few of the newly reported genetic variations relevant in MS have been replicated or correlated for clinical/paraclinical phenotypes such as spinal cord atrophy in independent patient cohorts. We genotyped 141 MS patients for 58 variations reported to reach significance in GWAS. Expanded disability status scale (EDSS) and disease duration (DD) are available from regular clinical examinations. MRI included sagittal high-resolution 3D T1-weighted magnetization-prepared rapid acquisition gradient echo of the cervical cord region used for volumetry. Due dependency of mean upper cervical cord area (MUCCA) with EDSS and/or DD, correction operations were performed compensating for EDSS/DD. We assessed each MS risk locus for possible MUCCA association. We identified twelve risk loci that significantly correlated with MUCCA. For nine loci-BAT, CYP27B1, IL12B, NFKB1, IL7, PLEK, EVI5, TAGAP and nrs669607-patients revealed significantly higher degree of atrophy; TYK2, RGS1 and CLEC16A revealed inverse effects. The weighted genetic risk score over the twelve loci showed significant correlation with MUCCA. Our data reveal a risk gene depending paraclinical/clinical phenotype. Since MUCCA clearly correlates with disability, the candidates identified here may serve as prognostic markers for disability progression

Will genetic variants correlate with MS susceptibility?

Studying groups of many thousands of people with MS,they have found over 150 genes associating with susceptibility but these have not really distinguished RRMSers vs PPMSers

In this study they looked at genetic variants in about 150 people and correlated this with size of the spinal cord and suggested that some correlate expression certain gene variants. Some of them are immune genes and one could spend hours trying to put a hypothesis around them, and if you want to try go to Wiki and see what these genes do, however is it worth it.

A few senior people studying genetics indicated that if the you don't study thousands of people the genetic analysis is usually quite meaning less. If this is so, maybe the genetics community should decide that the community shouldn't accept such genetic studies if they are not sizable enough, to save a deluge of unreproducible stuff. So when you see study claiming this or that effect. See how big the study is. Itmay helpyou work out if it may be correct or not 

Would this mean there was a monoculture of a few doing all the work....and getting all the grants.

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