Monthly Archives: August 2016

  • Protection against risk of Parkinson’s disease

    Parkinson’s disease was described in 1817 by Dr James Parkinson, who published an essay reporting six cases of ‘paralysis agitans’ (the disorder that was later renamed after Parkinson). He described the characteristic resting tremor, abnormal posture and gait, paralysis and diminished muscle strength, and the way that the disease progresses over time. [1]

    Since the advent of genetic testing several genes have been found to be associated with Parkinson’s disease (PD), resulting in various classifications. Autosomal dominant Parkinson disease type 8 (PARK8) is caused by heterozygous mutation in LRRK2, the gene encoding the dardarin protein. [2] The G2019S variant is one of the most common genetic causes of PD. Although the clinical motor signs of PD in carriers of the G2019S mutation are largely typical, an earlier age at onset of motor symptoms has been reported in some studies. [3]

    The word dardarin was taken from a Basque word for tremor, as the gene was first identified in families from England and the north of Spain. Mutations in LRRK2 are the most common known cause of familial and sporadic PD, accounting for approximately 5% of individuals with a family history of the disease and 3% of sporadic cases. They account for up to 10% of autosomal dominant familial and 3.6% of sporadic PD. More than 40 different variants, almost all missense, have been found. Seven seem to be proven pathogenic mutations, and are clustered in functionally important regions which are highly conserved through evolution. [4]

    23andMe carried out a privately-funded genome-wide association study (GWAS) to search for novel genetic variants associated with PD. The results, which were published in PLOS in 2011, replicated existing associations and discovered two novel variants. [5] In addition, 23andMe researched genes conferring protection on those with high-risk genes. [6] They found that of the approximately 1 in 10,000 people who have the G2019S  variant, those who also had a mutation in SGK1 were found to have a lower risk of PD than those with just the G2019S variant, conferring protection against the increased risk of PD. [7]

    Other causes of, or factors contributing to PD include pesticide exposure, [8] head trauma, medication, prolonged oxidative stress from infection or high homocysteine. Genetic factors include increased function of MAOB enzymes, high histamine from HNMT mutations, elevated L-dopa from DDC mutations or B6 deficiency. The Opus 23 software contains algorithms for Parkinson’s disease associated with some of these genetic causes, risk or contributory factors found in the 23andMe raw data. A new algorithm added to the Opus 23 Lumen app looks for both the LRRK2 G2019S and the SGK1 variants to assess for both risk of PD and protection from the risk genotype, and lists natural agents associated with gene function.


    1. Parkinson J. An essay on the shaking palsy. London: Sherwood, Neely and Jones; 1817.
    2. Kachergus J, Mata IF, Hulihan M, et. al. Identification of a novel LRRK2 mutation linked to autosomal dominant parkinsonism: evidence of a common founder  across European populations. Am J Hum Genet. 2005 Apr;76(4):672-80. Epub 2005 Feb 22. PMCID: PMC1199304.
    3. Thaler A, Mirelman A, Gurevich T,  et. al. Lower cognitive performance in healthy G2019S LRRK2 mutation carriers. Neurology. 2012 Sep 4;79(10):1027-32. PMCID: PMC3430708.
    4. Davie CA (2008). “A review of Parkinson’s disease”. Br. Med. Bull. 86 (1): 109–27. PMID 18398010
    5. Do CB, Tung JY, Dorfman E, et. al. Web-based genome-wide association study identifies two novel loci and a substantial genetic component for Parkinson’s disease. PLoS Genet. 2011 Jun;7(6):e1002141. PMCID: PMC3121750
    6. 23andMe Blog: 23andMe Discovers Genetic Variant That May Protect Those at High Risk for Parkinson’s Disease. Accessed Aug 28, 2016.
    7. Polymorphisms associated with Parkinson’s disease. Patent US8187811 B2.
    8. Van Maele-Fabry G, Hoet P, Vilain F, Lison D. Occupational exposure to pesticides and Parkinson’s disease: a systematic review and meta-analysis of cohort studies. Environ Int. October 2012, 46: 30–43. PMID: 22698719.


  • Kava-kava for panic attacks

    A 2008 paper by Thoeringer et. al., published in the Journal of Neural Transmission [1] described a study of 238 adult Caucasian patients recruited from an Anxiety Disorders Outpatient Clinic in Europe presenting various anxiety disorders, including panic disorder, agoraphobia, social phobia and generalized anxiety disorder. As there are many genetic studies linking the GABA system to anxiety disorders and related personality traits, the patients were genotyped for various polymorphisms in the SLC6A1 (GABA transporter 1), along with 267 controls without anxiety disorder.

    Five polymorphisms in SLC6A1 or in the promoter region were found to be nominally associated with anxiety disorders. Although none were statistically significant alone, the authors found a significant combined effect of all investigated polymorphisms, which strongly suggested a major role of SLC6A1 in the genetic susceptibility of pathological anxiety. Looking at patients with panic disorder, those with the most severe panic disorder were significantly more likely than controls to have two related polymorphisms in the SLC6A1.

    GABA (gamma-aminobutyric acid) is a neurotransmitter that decreases activity in the neurons of the brain and inhibits the excitability of nerve cells. Drugs that block the GABA transporter molecule inhibit the removal of GABA from the nerve synapses, thereby prolonging the action of GABA. Tiagabine, a selective GABA transporter 1 blocker, is used as an antiepileptic, but has off-label use for anxiety disorder. This is thought to be due to the augmentation of GABA function as a neurotransmitter in the brain. This drug has side-effects, however, and other methods of reducing panic disorder have been investigated.

    Kava-kava (Piper methysticum) is a traditional plant-based medicine found in the Western Pacific region which has been shown to reduce anxiety. Kava-kava is legal in most countries, and is generally safe when the root from a ‘noble’ cultivar is used. A study of kava-kava for anxiety reduction using the Hamilton Anxiety Rating Scale (HAMA) as the primary outcome found that patients with generalized anxiety disorder who had polymorphisms in SLC6A1 and in the 5′ flanking region potentially responded to kava-kava supplementation with a more significant reduction in HAMA rating than in patients without the polymorphisms. [2] Treatment consisted of tablets standardized to contain 60 mg of  kavalactones per tablet for a total daily dose of 120 mg of kavalactones for the first 3-week controlled phase, being titrated to 240 mg of kavalactones in nonresponse at the 3-week mark for the second 3-week controlled phase, or placebo.

    An algorithm in the Lumen app in Opus 23 determines how many relevant SNPs a client has in SLC6A1 that are reported in their 23andMe raw data, and which may make treatment with kava-kava more effective in reducing anxiety disorder and panic symptoms.


    1. Thoeringer, C.K., Ripke, S., Unschuld, P.G. et al. The GABA transporter 1 (SLC6A1): a novel candidate gene for anxiety disorders. J Neural Transm (2009) 116: 649. doi:10.1007/s00702-008-0075-y. PMCID: PMC2694916
    2. Sarris J, Stough C, Bousman CA, Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study. J Clin Psychopharmacol. 2013 Oct;33(5):643-8. doi: 10.1097/JCP.0b013e318291be67. PMID: 23635869