Introduction
DLB Genetics Has Remained Largely Elusive
Study type | Gene(s) or variant analysed | Ethnicity, population | Cases | Controls | Clinically or pathologically diagnosed DLB | DLB diagnostic criteria | Main finding | Ref. |
---|---|---|---|---|---|---|---|---|
Candidate gene |
C9orf72
| Caucasian—North American | 111 DLB* | 0 | All with pathological diagnosis—86 neocortical, 25 transitional. 66% met pathological criteria for AD | 2005 | No expansions > 30 repeats found | [17] |
Candidate gene |
C9orf72
| Caucasian—UK | 102 DLB | 0 | All with clinical diagnosis—probable DLB | 2005 | 2 clinical DLB with > 30 repeats | [18] |
Candidate gene |
C9orf72
| Caucasian—European, American, Australian | 1524 DLB*** | 0 | 1398 pathologically, 126 clinically diagnosed | 2005 | C9orf72 repeat expansions not common in pathologically diagnosed DLB | [19] |
Candidate gene | ADORA1 sequencing | Caucasian—North American | 111 DLB* and 1214 PD cases | 4911 | All DLB pathologically diagnosed—86 neocortical, 25 transitional | 2005 | ADORA1 variants not common in PD or DLB | [20] |
Candidate gene | Exon 24 of DNAJC13 | Caucasian—US, European | 1938 PD, 828 LBD | 0 | 1938 clinical PD, 828 pathologically diagnosed LBD | 2005 | Did not find p.Asn855Ser in any cases | [21] |
Candidate gene | TREM2 p.Arg47His | Caucasian—American | 1271 total LBD | 1154 | 442 clinical DLB cases, 829 pathologically diagnosed LBD cases: high (349), intermediate (254), and low clinical DLB likelihood (226) | 2005 | p.Arg47His not associated with DLB | [22] |
Candidate gene | RAB39B sequencing | Caucasian—American | 884 PD, 399 DLB and 379 LBD** | 0 | Clinical DLB, pathologically diagnosed LBD | Unclear, 2005 (?) | No coding variants found | [23] |
Candidate gene | MAPT haplotype genotyping | Caucasian—American | 731 DLB** | 1049 | 431 clinically diagnosed, 347 pathologically diagnosed (high-likelihood) | Clinical 2005 1996, pathological - 2005 | MAPT H1G haplotype suggested to be associated with DLB | [24] |
Candidate gene | MAPT p.Ala152Thr | Caucasian —American, European | 3229 PD, 442 DLB, 181 MSA and 832 LBD** | 2456 | All clinical DLB | 2005 | p.Ala152Thr suggested to be associated with DLB and LBD | [25] |
Candidate gene | Certain LRRK2 variants | Caucasian—American | 725 total DLB** | 1790 | 417 clinical DLB (384 probable DLB, 33 possible DLB), 355 pathologically diagnosed high likelihood DLB. (47 cases in both) | 2005 | No significantly associated LRRK2 variants with DLB | [26] |
Candidate genes (multiple) | GBA, LRRK2, MAPT, APOE, APP, PSEN1, PSEN2, SCARB2 and SNCA | Caucasian—North American | 111 DLB* | 222 neuro normal | All pathologically diagnosed—86 neocortical, 25 transitional 69% also met pathological criteria for AD | 2005 | Several variants identified | [27] |
Candidate genes (multiple) | PD and AD loci | Caucasian—European, American, Australian | 788 DLB*** | 2624 | 667 pathologically diagnosed | 2005 | SNCA, APOE significantly associated with DLB, whilst. SCARB2 showed suggestive association | [28] |
Candidate genes (multiple) | CNV analysis: APP, SNCA, PARK2. Selected exons: APP, LRRK2. Majority of exons: PSEN1, PSEN2, MAPT, GRN, TARBP, SNCA, PARK2, PINK1, DJ-1, APOE and GBA | Caucasian—Belgian | 99 DLB and 75 PDD | 626 | Majority clinically diagnosed | 2005 | Several variants identified | [29] |
Candidate genes (multiple) |
SNCA, LRRK2, UCHL1, GIGYF2, Omi/HTRA2, EIF4G1, PARK2, PINK1, ATP13A2, PLA2G6, FBX07, DJ-1, APP, PSEN1, PSEN2, C9orf72, SOD1, MAPT, PGRN, TARDBP, OPTN, ANG, CHMP2B, SQSTM1, FUS, VCP, OPTN
| Not reported, likely Caucasian—UK | 91 DLB | 93 | All pathologically diagnosed | 2005 | Several variants identified | [30] |
Candidate genes (several) | 43 tagging SNPs at the SNCA locus, SNCA dosage, APOE genotype | Caucasian—European, North American | 1492 PD and 922 DLB | 971 | 518/922 DLB pathologically diagnosed | 2005 | Dementia associated 5′ parkinsonism associated 3′ of SNCA | [31] |
Genetic analysis | Exome sequencing, APOE genotyping, C9ORF72 repeat analysis, CNV analysis | Likely Caucasian, not confirmed—UK | 289 AD, 252 FTD/ALS, 239 CJD, 39 PD, 58 DLB, 266 other neurodegenerative disease, 368 controls | 266 brains, 380 total controls used for association analysis | All DLB pathologically diagnosed | 2005 | TREM2 p.Arg62His and GRN rare variants suggested to be associated with DLB | [32] |
GWAS | Genome-wide genotyping | Caucasian—European, North American, Australian | 1743 DLB*** | 4454 | 1324 pathologically diagnosed, intermediate to high likelihood of DLB | 2005 | SNCA, APOE, GBA were genome-wide significantly associated with DLB | [16••] |