Pathway-Wide Genetic Risks in Chlamydial Infections Overlap between Tissue Tropisms: A Genome-Wide Association Scan

<div>Results of GWAS analysis for <i>Chlamydia trachomatis</i> seropositivity using EMMAX. (a) Manhattan plot showing index SNPs with <span class="nowrap"><svg height="11.7782pt" id="M31" style="vertical-align:-3.42938pt" version="1.1" viewbox="-0.0498162 -8.34882 102.523 11.7782" width="102.523pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M570 304C570 398 525 448 414 448C385 448 343 445 312 434L329 511L321 518C297 504 262 482 244 460L233 411C195 397 159 381 128 358L135 332C160 347 189 360 224 373L111 -147C97 -210 84 -218 17 -231L13 -257L254 -247L259 -218L233 -216C183 -212 177 -202 189 -142L218 -1C238 -10 266 -12 283 -12C351 3 429 48 483 105C543 168 570 242 570 304ZM482 289C482 161 380 33 304 33C278 33 248 51 233 69L303 396C326 400 352 403 369 403C428 403 482 380 482 289Z" id="g113-113"></path></g><g transform="matrix(.0091,0,0,-0.0091,7.384,3.132)"><path d="M522 166C507 123 488 90 472 71C449 44 419 38 347 38C296 38 261 38 242 51C223 63 217 85 217 132V315H311C398 315 406 310 419 239H453V433H419C406 365 401 358 311 358H217V580C217 609 219 612 251 612H331C400 612 427 604 440 584C453 561 463 541 472 498L506 502C501 558 497 627 497 650H43V618C122 610 130 609 130 520V128C130 46 121 40 30 32V0H521C529 30 552 128 557 162L522 166Z" id="g58-67"></path></g><g transform="matrix(.0091,0,0,-0.0091,12.662,3.132)"><path d="M871 0V33C783 41 780 45 777 152L768 506C765 610 771 609 860 617V650H683L453 157L228 650H59V617C150 609 154 606 146 481L132 275C124 170 117 125 112 93C105 50 84 39 27 34V0H267V34C200 39 176 48 173 93C170 130 171 172 176 256L190 540H192L414 8H438L682 554H685L689 152C689 45 686 41 604 33V0H871Z" id="g58-75"></path></g><g transform="matrix(.0091,0,0,-0.0091,20.87,3.132)"><path d="M871 0V33C783 41 780 45 777 152L768 506C765 610 771 609 860 617V650H683L453 157L228 650H59V617C150 609 154 606 146 481L132 275C124 170 117 125 112 93C105 50 84 39 27 34V0H267V34C200 39 176 48 173 93C170 130 171 172 176 256L190 540H192L414 8H438L682 554H685L689 152C689 45 686 41 604 33V0H871Z" id="g58-75"></path></g><g transform="matrix(.0091,0,0,-0.0091,29.078,3.132)"><path d="M682 0V33C615 38 603 49 571 134C507 305 441 494 378 665L343 655L136 136C101 48 86 41 22 33V0H246V33C170 41 161 50 183 112C196 152 209 192 224 232H441C461 176 478 126 493 87C504 49 499 41 433 33V0H682ZM425 279H242C273 363 303 448 335 533H337L425 279Z" id="g58-63"></path></g><g transform="matrix(.0091,0,0,-0.0091,35.476,3.132)"><path d="M665 0V33C595 38 568 55 523 124C476 196 422 278 366 366C436 471 466 514 487 540C533 599 553 609 628 617V650H396V617C459 610 463 599 440 558C413 507 382 460 343 400C300 467 263 522 232 575C216 602 218 609 278 617V650H27V617C100 609 114 598 160 531C193 479 239 409 291 325C206 194 151 118 127 89C99 53 67 38 8 33V0H242V33C177 41 172 50 196 91C229 151 269 219 316 288C380 189 422 120 446 81C465 49 459 38 398 33V0H665Z" id="g58-86"></path></g><g transform="matrix(.013,0,0,-0.013,45.794,0)"><path d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z" id="g117-91"></path></g><g transform="matrix(.013,0,0,-0.013,57.057,0)"><path d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z" id="g113-50"></path></g><g transform="matrix(.013,0,0,-0.013,66.203,0)"><path d="M528 54L331 254L528 455L492 493L294 291L96 493L60 455L257 254L60 54L96 16L294 217L492 16L528 54Z" id="g117-42"></path></g><g transform="matrix(.013,0,0,-0.013,76.739,0)"><path d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z" id="g113-50"></path></g><g transform="matrix(.013,0,0,-0.013,82.979,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z" id="g113-49"></path></g><g transform="matrix(.013,0,0,-0.013,89.219,0)"><path d="M469 201V252H50V201H469Z" id="g190-178"></path></g><g transform="matrix(.013,0,0,-0.013,96.004,0)"><path d="M137 343C167 482 260 545 321 574C357 591 397 603 429 609L423 641C382 634 335 622 295 608C189 570 37 457 37 238C37 84 125 -12 242 -12C362 -12 447 89 447 209C447 311 374 393 267 393C247 393 226 386 204 376L137 343ZM227 337C318 337 361 256 361 173C361 105 336 22 258 22C176 22 126 120 126 240C126 266 127 291 132 310C155 323 189 337 227 337Z" id="g113-55"></path></g></svg>.</span> There were two regions of within-gene SNP association with <i>Chlamydia trachomatis</i> serological response. (b) The Chr 7: 34560375–34666861 region, within the nonprotein-coding NPSR1 antisense RNA 1 (<i>NPSR1-AS1</i>) and immediately upstream of the G protein-coupled receptor coding neuropeptide S receptor 1 (<i>NPSR1</i>). (c) The Chr 10: 53873323–56733116 region, within the gene encoding protein kinase, CGMP-dependent, type I (<i>PRKG1</i>), a mediator of the nitric oxide/cGMP signalling pathway, which has roles in immune function and GPCR signalling.</div>

Mediators of Inflammation

fig1

Figure 1

Figure 1: Pathway-Wide Genetic Risks in Chlamydial Infections Overlap between Tissue Tropisms: A Genome-Wide Association Scan 