Genome-phenome wide association study of broadly defined headache.

Until recently, most genetic studies of headache have been conducted on participants with European ancestry. We therefore conducted a large-scale genome-wide association study of self-reported headache in individuals of East Asian ancestry (specifically those who were identified as Han Chinese). In this study, 108 855 participants were enrolled, including 12 026 headache cases from the Taiwan Biobank. For broadly defined headache phenotype, we identified a locus on Chromosome 17, with the lead single-nucleotide polymorphism rs8072917 (odds ratio 1.08, P = 4.49 × 10-8), mapped to two protein-coding genes RNF213 and ENDOV. For severe headache phenotype, we found a strong association on Chromosome 8, with the lead single-nucleotide polymorphism rs13272202 (odds ratio 1.30, P = 1.02 × 10-9), mapped to gene RP11-1101K5.1. We then conducted a conditional analysis and a statistical fine-mapping of the broadly defined headache-associated loci and identified a single credible set of loci with rs8072917 supporting that this lead variant was the true causal variant on RNF213 gene region. RNF213 replicated the result of previous studies and played important roles in the biological mechanism of broadly defined headache. On the basis of the previous results found in the Taiwan Biobank, we conducted phenome-wide association studies for the lead variants using data from the UK Biobank and found that the causal variant (single-nucleotide polymorphism rs8072917) was associated with muscle symptoms, cellulitis and abscess of face and neck, and cardiogenic shock. Our findings foster the genetic architecture of headache in individuals of East Asian ancestry. Our study can be replicated using genomic data linked to electronic health records from a variety of countries, therefore affecting a wide range of ethnicities globally. Our genome-phenome association study may facilitate the development of new genetic tests and novel drug mechanisms.

A Long-Term Study of Alignment Correction Following Proximal Femoral Varus Osteotomy and Pemberton Osteotomy in Children With Legg-Calvé-Perthes Disease and Developmental Dysplasia of the Hip.

Proximal femoral varus osteotomy (PFVO) is a common procedure performed in children with developmental dysplasia of the hip (DDH) and Legg-Calvé-Perthes disease (LCPD). However, the long-term effect on angular deformities of the knees and ankles following PFVO remains controversial. This study investigated the relationship between PFVO and alignment changes in the knee and ankle after the procedure. Twenty-five patients undergoing PFVO procedure with a minimum 4-year evaluation period were enrolled in the study, including 14 unilateral LCPD and 11 unilateral DDH. The standing scanogram examinations were collected before the operation, immediately following surgery, after a 1-year follow-up, after a 3-year follow-up, and at the final visit to the clinic. The radiographic parameters included leg length, femoral neck-shaft angle (FNSA), femorotibial angle (FTA), mechanical axis deviation (MAD), tibiotalar angle (TTA), and mechanical lateral distal femoral angle (mLDFA). At the final examination, FNSA demonstrated insignificant change between the operative and non-operative limbs in the DDH group. Compared with the postoperative result, FNSA significantly improved in the LCPD group (p = 0.039). Both groups did not develop statistical significance in TTA, mLDFA, MAD, and leg length discrepancy after more than a 5-year follow-up. From a biomechanical perspective that the foot passes more medial to the knee under the center of leg mass, varus knee was prone to develop. In order to correct the mechanical axis, the knee reverted to a valgus position gradually. Our study indicates that patients with LCPD or DDH receiving PFVO and Pemberton osteotomy narrow the gap of angular growth in knees and ankles between the operative and non-operative limbs after a long-term follow-up.

Tibial Lengthening along Submuscular Plate with Simultaneous Acute Tibial Deformity Correction by High-Energy Osteotomy: A Comparative Study.

Submuscular plating and osteotomy using power saw have shown the benefits in certain situations of limb lengthening. However, no previous studies combining both procedures have been conducted for acute tibial deformity correction and limb lengthening. Nineteen cases were enrolled in this study. Ten patients received tibial lengthening with acute knee angular deformity correction using high-energy osteotomy (Group 1), and nine patients received tibial lengthening only with osteotomy using multiple drills and osteotome (Group 2). Radiographic parameters retrieved before and after the operation included leg-length discrepancy, tibial length, length gained, mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle (MPTA), and mechanical axis deviation (MAD). There were significant differences between groups in terms of external fixator index (EFI) (p = 0.013) and healing index (HI) (p = 0.014), but no significance in the length gained (p = 0.356). The latest postoperative mLDFA (p = 0.315), MPTA (p = 0.497), and MAD (p = 0.211) of Group 1 were not distinguishable from Group 2. The functional outcomes were excellent, and there were no permanent complications. Despite showing a longer healing time, this alternative lengthening procedure which combines fixator-assisted plate lengthening in the tibia with simultaneous surgical intervention of acute tibial deformity correction using an oscillating saw is appropriate for patients with leg-length discrepancy and angular deformity of the tibia.