title: Exome sequencing and subsequent association studies identify five amino acid-altering variants influencing human height.
abstract: Height is a highly heritable trait that involves multiple genetic loci. To identify causal variants that influence stature, we sequenced whole exomes of four children with idiopathic short stature. Ninety-five nonsynonymous single-nucleotide polymorphisms (nsSNPs) were selected as potential candidate variants. We performed association analysis in 740 cohort individuals and identified 11 nsSNPs in 10 loci (DIS3L2, ZBTB38, FAM154A, PTCH1, TSSC4, KIF18A, GPR133, ACAN, FAM59A, and NINL) associated with adult height (P < 0.05), including five novel loci. Of these, two nsSNPs (TSSC4 and KIF18A loci) were significant at P < 0.05 in the replication study (n = 1,000) and five (ZBTB38, FAM154A, TSSC4, KIF18A, and FAM59A loci) were significant at P < 0.01 in the combined analysis (n = 1,740). Together, the five nsSNPs accounted for approximately 2.5% of the height variation. This study demonstrated the utility of next-generation sequencing in identifying genetic variants and loci associated with complex traits.
authors.affiliation: Asan Institute for Life Sciences, University of Ulsan College of Medicine, 388-1 Pungnap-2-Dong, Songpa-Gu, Seoul, 138-736, Korea.
authors.forename: Jae-Jung
authors.initials: JJ
authors.lastname: Kim
authors.forename: Young-Mi
authors.initials: YM
authors.lastname: Park
authors.forename: Kyu-Heum
authors.initials: KH
authors.lastname: Baik
authors.forename: Hye-Yeon
authors.initials: HY
authors.lastname: Choi
authors.forename: Gap-Seok
authors.initials: GS
authors.lastname: Yang
authors.forename: InSong
authors.initials: I
authors.lastname: Koh
authors.forename: Jung-Ah
authors.initials: JA
authors.lastname: Hwang
authors.forename: Jieun
authors.initials: J
authors.lastname: Lee
authors.forename: Yeon-Su
authors.initials: YS
authors.lastname: Lee
authors.forename: Hwanseok
authors.initials: H
authors.lastname: Rhee
authors.forename: Tae Soo
authors.initials: TS
authors.lastname: Kwon
authors.forename: Bok-Ghee
authors.initials: BG
authors.lastname: Han
authors.forename: Karen E
authors.initials: KE
authors.lastname: Heath
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.forename: Han-Wook
authors.initials: HW
authors.lastname: Yoo
authors.forename: Kiejung
authors.initials: K
authors.lastname: Park
authors.forename: Jong-Keuk
authors.initials: JK
authors.lastname: Lee
mesh_terms: D001827:Body Height / Q000235:genetics*; D059472:Exome; D005260:Female; D020869:Gene Expression Profiling; D015894:Genome, Human; D006130:Growth Disorders / Q000235:genetics; D006801:Humans; D007723:Korea; D008297:Male; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA