Replication of a genome-wide association study of panic disorder in a Japanese population

AbstractNumerous genetic variants associated with hypertension and blood pressure are known, but there is a paucity of evidence from genetic studies of resistant hypertension, especially in Asian populations. To identify novel genetic loci associated with resistant hypertension in the Japanese population, we conducted a genome-wide association study with 2705 resistant hypertension cases and 21,296 mild hypertension controls, all from BioBank Japan. We identified one novel susceptibility candidate locus, rs1442386 on chromosome 18p11.3 (DLGAP1), achieving genome-wide significance (odds ratio (95% CI) = 0.85 (0.81–0.90), P = 3.75 × 10−8) and 18 loci showing suggestive association, including rs62525059 of 8q24.3 (CYP11B2) and rs3774427 of 3p21.1 (CACNA1D). We further detected biological processes associated with resistant hypertension, including chemical synaptic transmission, regulation of transmembrane transport, neuron development and neurological system processes, highlighting the importance of the nervous system. This study provides insights into the etiology of resistant hypertension in the Japanese population.

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Genome wide association study of HTLV-1–associated myelopathy/tropical spastic paraparesis in the Japanese population

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2004199118 ◽

2021 ◽

Vol 118 (11) ◽

pp. e2004199118

Author(s):

Marina Penova ◽

Shuji Kawaguchi ◽

Jun-ichirou Yasunaga ◽

Takahisa Kawaguchi ◽

Tomoo Sato ◽

...

Keyword(s):

Amino Acid ◽

Association Study ◽

Proviral Load ◽

Odds Ratio ◽

Japanese Population ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Genome Wide ◽

A Genome ◽

Increased Risk

HTLV-1–associated myelopathy (HAM/TSP) is a chronic and progressive inflammatory disease of the central nervous system. The aim of our study was to identify genetic determinants related to the onset of HAM/TSP in the Japanese population. We conducted a genome-wide association study comprising 753 HAM/TSP patients and 899 asymptomatic HTLV-1 carriers. We also performed comprehensive genotyping of HLA-A, -B, -C, -DPB1, -DQB1, and -DRB1 genes using next-generation sequencing technology for 651 HAM/TSP patients and 804 carriers. A strong association was observed in HLA class I (P = 1.54 × 10−9) and class II (P = 1.21 × 10−8) loci with HAM/TSP. Association analysis using HLA genotyping results showed that HLA-C*07:02 (P = 2.61 × 10−5), HLA-B*07:02 (P = 4.97 × 10−10), HLA-DRB1*01:01 (P = 1.15 × 10−9) and HLA-DQB1*05:01 (P = 2.30 × 10−9) were associated with disease risk, while HLA-B*40:06 (P = 3.03 × 10−5), HLA-DRB1*15:01 (P = 1.06 × 10−5) and HLA-DQB1*06:02 (P = 1.78 × 10−6) worked protectively. Logistic regression analysis identified amino acid position 7 in the G-BETA domain of HLA-DRB1 as strongly associated with HAM/TSP (P = 9.52 × 10−10); individuals homozygous for leucine had an associated increased risk of HAM/TSP (odds ratio, 9.57), and proline was protective (odds ratio, 0.65). Both associations were independent of the known risk associated with proviral load. DRB1-GB-7-Leu was not significantly associated with proviral load. We have identified DRB1-GB-7-Leu as a genetic risk factor for HAM/TSP development independent of proviral load. This suggests that the amino acid residue may serve as a specific marker to identify the risk of HAM/TSP even without knowledge of proviral load. In light of its allele frequency worldwide, this biomarker will likely prove useful in HTLV-1 endemic areas across the globe.

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